Stem Cell Research for Ischemic Stroke

Cells Used

• Cell Type: Human placenta-derived 3D mesenchymal stem/stromal cells.
• This means the cells are prepared using a 3D culture method, where the cells can grow in clusters or spheroids rather than only flat on a dish.
• Product Name: Guojianqingke / Guojiangqingke.
• Also listed as: 3D MSC – QK01.
• The cells are delivered through an IV.

Cell Preparation Before Infusion

• The product is stored frozen in liquid nitrogen.
• Before treatment, the product is thawed in a 37°C water bath.
• After thawing, 40 mL of cold compound electrolyte injection is added to the product bag.
• The product is mixed before infusion.

Treatment Groups

• Phase I: Dose escalation.
• This part is mainly about safety.
• Researchers give a single IV dose.
• The trial uses increasing dose levels.
• The aim is to find the maximum tolerated dose.
• This is the highest dose that can be given without unacceptable safety problems.
• The trial also aims to find the recommended Phase 2 dose.
• This is the dose they would use in the next stage.
• The exact dose numbers are not publicly listed in the trial record.

Phase IIa: Expansion Stage

• This part looks at early signs of effectiveness.
• Participants receive the recommended Phase 2 dose selected from Phase I.
• This part is randomized, double-blind, and placebo-controlled.

Placebo Group

• The placebo is cell culture medium without cells.
• It is given by IV.
• The placebo preparation and infusion process is designed to look similar to the cell treatment.

Main Question

• Can IV human placenta-derived 3D MSCs be used safely in people with acute ischemic stroke?
• Researchers also want to see whether there are early signs that patients recover better after treatment.

Main Outcome

• The main outcome is how many participants have an mRS score of 0 to 2 at Day 90 after treatment.
• mRS stands for modified Rankin Scale.
• It measures disability after stroke.
• A score of 0 to 2 usually means the person has no symptoms, mild symptoms, or can live independently despite some disability.
• So the main question is: By Day 90, how many people are functionally independent?

Other Recovery Checks

• Researchers also check mRS 0 to 2 at Day 28.
• They check mRS 0 to 2 at Day 180.
• They check mRS 0 to 2 at Day 270.
• They check mRS 0 to 2 at Day 360.
• This helps show whether recovery changes over time.

Safety Outcomes

• The trial checks for dose-limiting toxicity in Phase I.
• Dose-limiting toxicity means a side effect serious enough to stop dose increase or delay treatment.
• They define this as serious non-blood toxicity, serious blood toxicity lasting more than 7 days, or toxicity that delays dosing by more than 14 days.
• They also check serious adverse events from the first dose through Day 720.
• Serious adverse events include death, life-threatening events, hospitalization, disability, birth defects, or other medically important events.

How Safety Is Checked

• Physical examination.
• Vital signs.
• Blood tests.
• Blood chemistry.
• Coagulation tests.
• CT or MRI imaging.

Simple Version

• Were the cells safe?
• Did patients tolerate the IV infusion?
• What dose can be used?
• Did patients become less disabled?
• Did more patients become functionally independent?
• Did recovery last through later follow-ups?
• Were there serious side effects through 2 years?

Follow-up

• Participants are followed for up to 720 days.
• The main effectiveness check is at Day 90.
• Recovery is also checked at Day 28, Day 180, Day 270, and Day 360.
• Safety is tracked through Day 720.

Analysis

• Researchers will compare the stem cell group with the placebo group.
• They will look at whether IV placenta-derived 3D MSCs appear safe.
• They will also look for early signs that patients recovered better than those who received placebo.

Expected Completion

• Primary completion is listed as December 30, 2027.
• Final completion is listed as December 2028.

Cells used

• Cell type: Human umbilical cord-derived mesenchymal stem/stromal cells and delivered through an IV.
• The cells are expanded/cultured.

Treatment groups

• Phase Ia: Single IV dose
• Low dose: 50 million cells
• Medium dose: 100 million cells
• High dose: 200 million cells

Phase Ib: Multiple IV doses

• Two dose levels are selected based on Phase Ia results.
• Participants receive IV treatment on Day 0, Day 7, and Day 14.
• This means 3 IV doses total.

Placebo group

• The placebo is a cell-free product.
• It is designed to match the investigational product in packaging, storage, expiration date, and administration method.

What They’re Looking For

• The main thing researchers want to know is:
• Are IV umbilical cord-derived MSCs safe and tolerable in people with acute ischemic stroke?
• Because this is a Phase 1 trial, safety is the main focus.

They are checking for:

• Dose-limiting toxicities by Day 28.
• Adverse events and serious adverse events during the trial.
• Death from any cause at Day 90, Day 180, and Day 360.

They are also looking for early signs of recovery.

• They measure this using:
• mRS score: This looks at disability after stroke.
• They are checking how many people reach an mRS score of 0 to 2.
• That usually means the person has no symptoms, mild symptoms, or can live independently despite some disability.
• NIHSS score: This measures stroke severity.
• It looks at things like movement, speech, sensation, vision, and awareness.
• They are checking whether patients improve by at least 4 points. They are also checking the total change in NIHSS score from baseline.
• Barthel Index
• This looks at daily independence.
• It checks whether the person can do basic daily activities like eating, dressing, walking, toileting, and moving from bed to chair.
• They are checking how many participants reach a Barthel Index score of 95 or higher.
• Fugl-Meyer motor score
• This looks at movement recovery after stroke. A higher score means better motor function.
• CT/MRI imaging
• They are checking whether there are changes on brain imaging at Day 90.
• Immune response
• They are checking Human Leukocyte Antigen antibodies. This helps show whether the body is reacting immunologically to the donor umbilical cord cells.

They are not just asking, “Did the cells work?”

• They are asking:
• Were the cells safe? Did patients tolerate the IV treatment? Was there any immune reaction? Did patients show better stroke recovery? Did they become less disabled? Did movement improve? Did daily independence improve? Did brain imaging change?

Safety

• Safety is the main focus of the trial.
• The trial tracks dose-limiting toxicities, adverse events, serious adverse events, immune response, and death from any cause.

Follow-up

• Participants are followed for up to 2 years.
• Safety is checked early, including at Day 28 after dosing.
• Recovery is tracked at different time points, including Day 30, Day 90, Day 180, and Day 360.

Analysis

• Researchers will compare the stem cell groups with the placebo groups.
• They will look at whether IV umbilical cord-derived MSCs appear safe.
• They will also look for early signs that patients recovered better than those who received placebo.

Expected completion

• Primary completion is listed as March 30, 2028.
• Final completion is listed as November 30, 2029.

Procedure

• The study treatment is IxCell hUC-MSC-S.
• It is given by IV infusion.

Cells used

• Cell type: Human umbilical cord-derived mesenchymal stem cells.
• Whose cells: Allogeneic. This means the cells come from donor umbilical cord tissue, not from the patient.

Treatment groups

• Experimental group: IxCell hUC-MSC-S, given by IV infusion.
• Placebo group: placebo, given by IV infusion.
• The trial record does not give the cell dose.

What They’re Looking For

• The main thing researchers want to know is:
• Do people move better 12 months after stroke if they receive IxCell hUC-MSC-S, compared with placebo?
• They measure this using the Fugl-Meyer motor score, which is a stroke recovery test focused on movement. A higher score means better movement.
• They are also checking whether the treatment helps people become more independent in daily life.

To do this, they look at:

• Disability after stroke — whether the person is less dependent on others.
• Stroke severity — whether symptoms like weakness, speech problems, sensation, and vision improve.
• Daily activities — whether the person can do things like eating, dressing, walking, and using the toilet more independently.
• Thinking and memory — whether cognitive function changes after treatment.
• The study also includes blood vessel imaging and biomarker checks.

They are not just asking, “Did the cells work?”

• They are asking:
• Did the person move better, function better, need less help, think better and stay safe over 12 months?

Safety

• The trial will track safety during the 12-month study period.

Recruitment

• The trial is listed as not yet recruiting.

Follow-up

• Participants are followed for 12 months.
• The main recovery check happens at 12 months.
• Researchers track movement, disability, stroke severity, daily independence, thinking ability, vascular imaging, biomarkers, and safety.

Analysis

• After the follow-up period, researchers will compare the stem cell group with the placebo group.
• They will look to see whether people who received IxCell hUC-MSC-S had better recovery than people who received placebo.

Expected completion

• Primary completion is listed as June 30, 2027.
• Final completion is listed as December 31, 2027.

Procedure

• The study treatment is Adipose derived Stem Cell. It is given by IV (intravenous) treatment.

Cells used

• Cell type: Adipose-derived stem cells (ADSCs), which are stem cells obtained from fat tissue.
• Whose cells: Allogeneic: the cells come from a donor, not from the participant receiving them.
• Cultured or expanded: Yes

Treatment groups

• Experimental group: adipose-derived stem cells, 1,000,000 cells per kg, given by IV (intravenous).
• Experimental group: adipose-derived stem cells, 2,000,000 cells per kg, given by IV (intravenous).
• Experimental group: adipose-derived stem cells, 2,500,000 cells per kg, given by IV (intravenous).
• Experimental group: adipose-derived stem cells, 3,000,000 cells per kg, given by IV (intravenous).
• Placebo comparison group: placebo.
• The number shown is for each kilogram of body weight. The participant’s total cell number depends on their weight.

What They’re Looking For

• The researchers want to learn whether the treatment helps people recover and whether it is safe.

Independence after stroke

• The modified Rankin Scale (mRS) measures disability after stroke. It runs from 0, meaning no symptoms, to 6, meaning death.

Effect of different cell doses

• Researchers compare the cell doses to see whether a higher or lower dose is linked to better recovery. This is assessed over 6 months.

Stroke symptoms

• The NIH Stroke Scale (NIHSS) measures stroke severity. A lower score is better.

Daily life and movement

• The Barthel Index looks at everyday tasks such as eating, dressing, and walking. The Fugl-Meyer motor score measures movement recovery.

Brain activity

• The study also uses functional MRI. This may help researchers see whether brain activity changes after treatment.

Blood biomarkers

• The researchers also look at blood markers linked to stroke recovery. They want to see whether there are signs in the blood that may help explain recovery.

Safety

• The first part of the study looks at whether the cells cause any serious cell-related safety problems within 7 days after stroke. They also track adverse events and deaths over 2 years.

Recruitment

• The trial is listed as recruiting. Trial status can change, so it should be checked on the original registry before contacting a study site.

Follow-up

• Participants are followed for up to 2 years. Some of the main recovery checks happen at 6 months, but safety and longer-term stroke recovery are tracked over 2 years.
• Researchers track safety, disability, stroke severity, movement recovery, brain activity, and blood biomarkers.

Analysis

• After follow-up is complete, researchers will compare the treatment groups with the placebo group. They will look for differences in recovery, daily function, movement, and safety.

Expected completion

• Primary completion is listed as July 1, 2025. Final completion is listed as July 1, 2027.

Delivery Method:

• The cells are given by intravenous infusion.
• The treatment uses umbilical cord-derived mesenchymal stem cells. The product name is Neuroncell-EX.

Treatment Groups

• Stem Cell Group:
• Participants receive Neuroncell-EX.
• Dose: 2 million umbilical cord MSCs per kg of body weight.
• The treatment is given on Day 1 and Day 14.
• Participants also receive standard medical care for acute stroke.

Placebo Group:

• Participants receive placebo.
• The placebo is normal saline. This is also given by IV infusion on Day 1 and Day 14.
• Participants also receive standard medical care for acute stroke.

Blinding:

• Double-blind design.
• Participants and investigators do not know who received stem cells and who received placebo.

Duration:

• Participants are followed for up to 12 months.

What They’re Looking For

• The researchers are checking whether Neuroncell-EX helps people recover after an acute ischemic stroke.
• They are mainly measuring:

Daily function

• Can the person do basic daily activities after the stroke?
• This includes things like eating, moving, dressing, bathing, and using the toilet.
• They measure this using the Barthel Index.
• The Barthel Index score goes from 0 to 100.
• A higher score means the person is more independent.

Stroke disability

• How disabled is the person after the stroke?
• They measure this using the modified Rankin Scale, also called mRS.
• mRS is a score from 0 to 6.
• 0 means no symptoms.
• 6 means death.
• A lower score is better.
• The researchers compare mRS scores between the Neuroncell-EX group and the placebo group.

They measure Barthel Index and mRS at:

• Baseline
• 6 weeks
• 3 months
• 6 months
• 12 months

Safety

• The researchers are also checking whether the treatment causes any problems.
• This includes adverse events, sepsis, organ failure, hospitalization, cancers, and death during the study.

Survival and re-admission

• They are checking how many people survive during the study.
• They are also checking how many people are re-admitted to hospital.

Inflammation in the blood

• The researchers are also looking at blood markers linked to inflammation and repair.
• These include IL-6, IL-2, MMP-9, TNF-alpha, IL-1 beta, VEGF, IL-10, IL-1Ra, and TGF-beta 1.

Simple version:

• They want to see whether the treatment changes inflammation in the body after stroke.

Brain imaging

• The study also says researchers will use functional MRI.
• This may help them look at brain activity and recovery after treatment.

Recruitment:

• The trial is currently recruiting in Malaysia.
• The listed study site is Hospital Canselor Tuanku Muhriz UKM in Cheras, Kuala Lumpur.

Follow-up:

• Participants will be followed for up to 12 months.
• Researchers will track daily function, stroke disability, safety, survival, hospital re-admission, blood inflammatory markers, and brain imaging.

Analysis:

• After participants complete follow-up, researchers will compare the Neuroncell-EX group against the placebo group.
• They will look at whether people who received IV umbilical cord MSCs recover better than people who received placebo.
• They will also check whether the treatment appears safe.

Completion:

• Primary completion is expected in November 2026.
• Final study completion is expected in December 2026.

Delivery Method:

• The cells are given by intravenous infusion.
• The treatment uses human umbilical cord mesenchymal stem cells.

Treatment Groups

• High-Dose Single Infusion Group:
• Participants receive one IV infusion of hUC-MSCs on Day 0.
• Dose: 200 million cells total.
• They then receive placebo cell medium on Day 7 and Day 14.

Low-Dose Multiple Infusion Group:

• Participants receive three IV infusions of hUC-MSCs.
• Dose: 100 million cells per infusion.
• Total dose: 300 million cells across three infusions.

Placebo Group:

• Participants receive placebo cell medium.

Blinding:

• Double-blind design.
• Participants and investigators assessing the results do not know who received stem cells and who received placebo.

Duration:

• Participants are followed for up to 360 days after treatment.

What They’re Looking For

• The researchers are checking whether the treatment helps people recover after an acute ischemic stroke.
• They are mainly measuring:

Independence after stroke

• Can the person live independently, or close to independently, after treatment?
• They measure this using mRS, a stroke disability score from 0 to 6.
• 0 = no symptoms. 6 = death.
• The key target is mRS 0 to 2.

Stroke symptom improvement

• Are the person’s stroke symptoms getting better?
• They measure this using NIHSS, a stroke severity score.
• A lower score is better.
• They check whether patients improve by at least 4 points.

Daily function

• Can the person do basic daily tasks like walking, eating, dressing, bathing, and using the toilet?
• They measure this using the Barthel Index.
• A score of 95 or higher usually means the person is mostly independent.

Movement recovery

• Is the person’s movement improving after the stroke?
• They measure this using the Fugl-Meyer motor score.
• A higher score means better movement.

Safety

• They are also checking whether the treatment causes any problems.
• This includes side effects, serious side effects, worsening stroke symptoms, or deaths during the study.

Recruitment:

• The trial is currently recruiting in China.
• The listed study site is Beijing Tiantan Hospital, Capital Medical University, in Beijing.

Follow-up:

• Participants will be followed for up to 360 days.
• Researchers will track disability, stroke severity, independence, movement recovery, safety, and mortality.

Analysis:

• After participants complete follow-up, researchers will compare the stem cell groups against placebo.
• They will look at whether IV umbilical cord MSCs help more patients recover independence and improve stroke symptoms.
• They will also compare the single high-dose treatment against the repeated lower-dose treatment.

Completion:

• Primary completion is expected in March 2026.
• Final study completion is expected in December 2026.

Stem Cell Type:

• The treatment uses autologous mesenchymal stem cells.
• In this trial, the cells come from the patient’s bone marrow. The final stem cell product is called HUNS001-01.

Delivery Method:

• The stem cells are injected directly into the brain. This is called intracerebral transplantation.
• Intracerebral means inside the brain.
• This is much more direct than giving cells through a normal IV drip.
• The cells are injected into 2 brain sites.

Why They Are Using This Delivery Method

• The brain is hard to reach.
• If cells are given through a normal IV drip, many of them may get trapped in other organs before reaching the brain.
• It is placing the cells directly into the brain near the affected area.
• The idea is to get the treatment closer to the damaged brain tissue instead of relying on the cells to travel through the bloodstream.

Dose:

• Participants 40 million mesenchymal stem cells.
• The cells are injected into 2 brain sites.

Duration:

• Participants are followed for up to 1 year for the main outcome.
• The full study is expected to continue until November 2027.

What They’re Looking For

• The main thing researchers want to know is whether patients become less disabled after treatment.
• They are measuring this with a stroke disability score called the modified Rankin Scale, or mRS.
• A lower score is better. A higher score means more disability.
• In this trial, a patient counts as improved if their mRS score improves by at least 1 point after 1 year.
• For example, moving from mRS 4 to mRS 3 would count as improvement.
• Researchers are also checking whether the treatment causes safety problems.
• They are tracking adverse events for 1 year.
• They are also looking at whether patients improve in ways that matter in daily life.
• This includes whether stroke symptoms become less severe, whether movement improves, and whether the person can do more things for themselves.
• They measure this using stroke recovery tests such as NIHSS, FIM, Fugl-Meyer, and Barthel Index.
• The trial also uses brain scans to see whether anything changes in the affected area of the brain.
• These scans include FDG-PET and IMZ-SPECT.
• So the trial is checking whether patients become less disabled, whether the treatment is safe, whether movement and daily function improve, and whether brain scans show measurable changes.

Recruitment:

• The trial is currently recruiting.
• The plan is to recruit 8 participants in Japan.

Final takeaway:

• This trial is testing whether a patient’s own cultured bone marrow stem cells, injected directly into the brain, can help people with long-term disability after an ischemic stroke.

Stem Cell Type:

• The treatment uses autologous bone marrow-derived mesenchymal stem cells.
• The cells are expanded and cultured in a lab

Delivery Method:

• The stem cells are given back to the patient three times.
• The trial is testing two main delivery methods.

Delivery Method 1: Ommaya Reservoir

• An Ommaya reservoir is a small medical device placed under the scalp. This is a brain access device, closer to the brain and nervous system. This is a more direct method than a normal IV drip.
• It gives doctors a way to deliver treatment into the central nervous system.

Delivery Method 2: Internal Carotid Artery

• The internal carotid artery is one of the main blood vessels carrying blood to the brain.
• This is more targeted than putting cells into a normal vein.

Why They Are Using These Delivery Methods

• The brain is hard to reach because of the blood-brain barrier.
• The blood-brain barrier helps protect the brain, but it can also make it harder for treatments to get into brain tissue.
• If stem cells are given through a normal IV drip, many of them may get trapped in the lungs, liver, or spleen before reaching the brain.
• So this trial is using more targeted delivery methods.
• They are trying to get the cells closer to the brain instead of just putting them into a vein and hoping enough cells reach the damaged area.

Treatment Groups

• Group 1: Ommaya Reservoir Group
• Participants receive stem cells through an Ommaya reservoir.
• Dose:
• 20 million cells per dose.
• Because patients receive 3 infusions, the total dose is:
• 60 million cells total.

Group 2: Low-Dose Internal Carotid Artery Group

• Participants receive stem cells through the internal carotid artery.
• Dose:
• 2.5 million cells per dose.
• Because patients receive 3 infusions, the total dose is:
• 7.5 million cells total.

Group 3: High-Dose Internal Carotid Artery Group

• Participants receive stem cells through the internal carotid artery.
• Dose:
• 10 million cells per dose.
• Because patients receive 3 infusions, the total dose is:
• 30 million cells total.

Blinding:

• Double-blind design.
• Participants and investigators assessing outcomes do not know which group the participant is in.

Duration:

• Participants are followed after each transplantation and again at 6 months.

Primary Outcome

Safety:

• The main thing researchers are measuring is safety.
• They are tracking adverse events and serious adverse events.
• Adverse events are unwanted medical problems that happen during or after treatment.
• Serious adverse events are more serious problems, such as life-threatening events, hospitalization, major complications, or death.
• Researchers will check for safety problems:
• 3 to 7 days after each stem cell transplantation.
• At the 6-month follow-up.

Simple version:

• The main question is:
• Is this treatment safe enough to keep studying?

Secondary Outcomes

• The researchers are also checking whether patients improve after treatment.
• They are looking at:
• How severe the stroke symptoms are.
• How disabled or independent the person is.
• Whether they can do daily tasks more easily, like washing, dressing, eating, moving around, and using the toilet.
• Whether arm and leg movement improves.
• Whether balance improves.
• Whether walking improves, including walking speed and how much help the person needs to walk.
• Whether muscle activity changes.
• Whether the damaged area in the brain changes on MRI.
• The trial uses medical scoring systems to measure these changes, including NIHSS, mRS, Barthel Index, Fugl-Meyer, 10-Meter Walk Test, FAC, sEMG, and MRI.
• They are not just asking, “Did the patient feel better?”
• They are checking whether the person becomes safer, more mobile, more independent, and whether there are any measurable changes in the brain or muscle activity.

Recruitment:

• The trial is not yet recruiting.
• The plan is to recruit 12 participants in China.

Completion:

• The trial is expected to finish in May 2027.
• This is still an early-stage trial with only 12 participants. That means it is mainly testing safety and feasibility. It is not large enough to prove the treatment works.

Simple final takeaway:

• This trial is testing a patient’s own bone marrow stem cells for ischemic stroke. The cells are given back three times, either through a brain reservoir or through a major artery supplying the brain. The main goal is to see if the treatment is safe. Researchers will also look for early signs of improvement in movement, walking, disability, daily function, brain imaging, and muscle activity.

Procedure

• Patients received umbilical cord-derived mesenchymal stem cells.
• The cells were given through an IV.
• The dose was 100 million cells.
• The treatment was given as a single dose.

Placebo Group

• The study also had a placebo group.
• Patients in the placebo group received an IV placebo solution that looked the same as the treatment.
• The trial was randomized and double-blinded.
• It also lists quadruple masking, meaning the participant, care provider, investigator, and outcome assessor were masked.
• In simple terms, the patients and the people assessing them were not meant to know who received the stem cells and who received placebo.

What They Are Measuring

• The researchers mainly wanted to know whether patients became more independent after treatment.
• The main measurement was how many patients reached a modified Rankin Scale score of 0 to 2 at 90 days.
• The modified Rankin Scale, or mRS, is a disability score used after stroke.
• A score of 0 means no symptoms.
• A score of 6 means death.
• A lower score is better.
• An mRS score of 0 to 2 usually means the person is independent, or close to independent, in daily life.
• They also checked whether this improvement lasted at 180 and 360 days.

The researchers also measured:

• Movement recovery using the Fugl-Meyer score.
• Hand and arm function using the Purdue hand function test and box and block test.
• Stroke severity using the NIHSS score.
• Memory and thinking using the MMSE and MoCA scores.
• Brain imaging changes using FLAIR and DTI MRI scans.
• Blood marker changes, including CPEC, VEGF, BDNF, and MMP-9.
• Side effects or medical problems over 360 days.
• In simple terms, the researchers were checking whether one IV dose of 100 million umbilical cord-derived mesenchymal stem cells was safe, and whether patients recovered better after ischemic stroke compared with placebo.

Procedure

• Patients receive NR1 neural stem cells.
• The cells are injected directly into the brain.
• The trial uses escalating doses.
• That means different patient groups receive increasing doses of the cells.
• The study uses a traditional 3+3 trial design.
• In simple terms, that means researchers start with a small group at a lower dose, check safety, and then may move to a higher dose in the next group.

Delivery Method

• The cells are given by intracerebral administration. That means the cells are placed directly into the brain.

Cells Used

• The study uses NR1 neural stem cells.
• NR1 is described as a human embryonic stem cell-derived neural stem cell product.
• That means the product comes from human embryonic stem cells that have been turned into neural stem cells.

Immune Suppression

• Patients must be willing to take tacrolimus, also called Prograf.
• They take it 2 days before the transplant and for 2 months after the transplant.
• Tacrolimus is an immune-suppressing drug.

What They Are Measuring

• The researchers are mainly measuring:
• Treatment-emergent adverse events.
• Fugl-Meyer motor score.
• Treatment-emergent adverse events means side effects or medical problems that happen after the treatment.
• The trial measures these over 0 to 12 months.
• Fugl-Meyer motor score is a test used after stroke to measure movement and motor recovery.
• The trial is looking at whether the Fugl-Meyer motor score changes compared with baseline.
• Baseline means the patient’s score before treatment.
• The researchers are checking whether injecting NR1 neural stem cells directly into the brain is safe, and whether patients show early signs of improved movement after chronic stroke.

Procedure

• Patients are split into 3 groups:

Group 1:

• Conditioned medium plus umbilical cord MSCs.
• These patients receive conditioned medium through the nose for 3 days in a row.
• They also receive 20 million umbilical cord MSCs transplanted directly into the brain tissue.

Group 2:

• Umbilical cord MSCs only.
• These patients receive 20 million umbilical cord MSCs transplanted directly into the brain tissue.

Group 3:

• Standard stroke treatment.
• These patients receive standard neurological and neurotrophic drugs.

Delivery Method

• The conditioned medium is given intranasally, through the nose.
• The dose is 3 cc each time, for 3 days in a row.
• The umbilical cord MSCs are given by intraparenchymal transplantation. That means the cells are placed directly into the brain tissue.

Cells Used

• The study uses umbilical cord mesenchymal stem cells.
• UC-MSCs are being tested because researchers believe they may release signals that support brain repair after stroke.

Conditioned Medium / Secretome

• The study also uses conditioned medium. The trial also calls this secretome.
• Conditioned medium is not the same as live stem cells. It is the fluid that contains substances released by cells.
• The idea is that this fluid may contain biological signals that could support repair, recovery, or brain healing.

What They Are Measuring

• The researchers are mainly measuring:
• Brain-Derived Neurotrophic Factor, also called BDNF.
• Vascular Endothelial Growth Factor, also called VEGF.
• MRI changes in the brain.
• NIH Stroke Scale score.
• Modified Rankin Scale score.
• BDNF is a biological marker linked to nerve health and repair.
• VEGF is a biological marker linked to blood vessel growth and repair.
• NIHSS measures stroke-related neurological problems.
• mRS measures how disabled or independent someone is after a stroke.

MRI

• The trial says MRI is used to observe brain development, described as neurogenesis.

Procedure

• Patients were split into three groups:

IV UC-MSC group:

• 16 patients received umbilical cord-derived MSCs through a vein.

Intrathecal UC-MSC group:

• 16 patients received umbilical cord-derived MSCs into the spinal canal.

Control group:

• 16 patients received standard stroke rehabilitation only.

Dose

• Both stem cell groups received the same dose: 1.5 million cells per kg of body weight.
• So for example, a 70 kg patient would receive about 105 million cells per dose.
• They received 2 doses total: one at baseline and another 3 months later.

Delivery Method

• IV group:
• The cells were given through a peripheral vein.
• Intrathecal group:
• The cells were injected into the spinal canal at the L4-L5 level using a lumbar puncture technique.

Rehabilitation

• All groups could receive up to 30 rehabilitation sessions.
• The rehab included physical therapy, occupational therapy, and speech therapy depending on the patient’s needs.
• Each rehab session lasted around 60 minutes.

Cells Used

• The therapy used allogeneic umbilical cord-derived mesenchymal stem cells.
• The umbilical cords were screened for infectious diseases including:
• HIV
• Cytomegalovirus
• Epstein-Barr virus
• Hepatitis A
• Hepatitis B
• Hepatitis C
• Syphilis
• Chlamydia

Culture Method / Cell Preparation

• The UC-MSCs came from a master biobank, meaning a controlled cell bank created from donated umbilical cords.
• The researchers screened 30 umbilical cords from healthy full-term newborns.
• That cell line was expanded to passage 5, also called P5. This means the cells had gone through five rounds of lab growth before being used.
• The cells were frozen in CryoStore CS10, a freezing solution used to protect cells during storage.
• They were stored in liquid nitrogen vapor at -196°C until treatment.
• Before infusion, the cells were thawed, washed to remove the freezing solution, and mixed with Ringer’s lactate, a medical fluid used for infusion.
• Before the cells could be given to patients, the final UC-MSC product had to pass these safety checks:
• Viability: more than 70% of the cells had to be alive.
• Endotoxin level: ≤0.2 EU/kg body weight for intrathecal use and ≤5 EU/kg body weight for IV use.
• Contamination: no bacterial, fungal, or mycoplasma contamination.
• Positive MSC markers: CD73, CD90, and CD105 had to be ≥95%.
• Unwanted blood/immune cell markers: CD45, CD34, CD11b, CD19, and HLA-DR had to be ≤2%.

Follow-up Duration

• Patients were followed for 12 months.
• Assessments were done at:
• Baseline
• 3 months
• 6 months
• 12 months

Results

• Patients were followed for 12 months.
• The main outcome was safety.
• The researchers also looked at whether patients improved in stroke severity, daily independence, muscle stiffness, hand function, quality of life, and MRI brain blood flow.

Safety

• No serious adverse events were considered related to the UC-MSC treatment.
• There were 4 serious adverse events in total, but the researchers said they were unrelated to the cells.
• These included COVID-19 infection, gastrointestinal bleeding from a gastric ulcer, and mitral valve replacement.
• IV had fewer regular adverse events than intrathecal treatment.
• IV group:
• There were 4 adverse events, mostly mild headache and slight swelling/redness at the infusion site.
• Intrathecal group:
• There were 17 adverse events, mostly mild pain at the lumbar puncture site and headache.
• Simple takeaway:
• IV appeared safer and easier to tolerate because it avoids a lumbar puncture into the spinal canal.

Clinical Results

• By 12 months, both the IV and intrathecal groups improved more than the control group on several stroke recovery scores.
• Patients improved in:
• Stroke severity
• Daily independence
• Muscle stiffness/spasticity
• Hand and finger function
• Quality of life
• IV looked slightly better overall because it had fewer side effects and showed stronger or earlier improvements on some scores.
• But the study did not clearly prove that IV was statistically better than intrathecal in a direct head-to-head comparison.

MRI Imaging

• MRI results were weaker than the clinical results.
• The researchers used ASL MRI to look at brain blood flow.
• They did not mainly measure whether the stroke-damaged area got smaller.
• At 12 months, improved brain blood flow was seen in:
• 4 out of 16 IV patients
• 2 out of 16 intrathecal patients
• 3 out of 16 control patients
• This was not statistically significant.
• Simple takeaway:
• Patients seemed to function better, but the MRI brain blood-flow results did not clearly prove a strong imaging improvement.

How the Cells Worked

• The researchers did not prove exactly how the cells worked in this trial.
• They believed UC-MSCs may help stroke recovery by calming inflammation, protecting damaged brain tissue, supporting repair, and helping the brain adapt after injury.
• They also looked at whether the cells could improve brain blood flow using ASL MRI, but the MRI results were not clearly positive.
• Important:
• The study did not prove that the cells rebuilt the brain, replaced dead brain cells, or made the stroke-damaged area smaller.
• The study mainly showed better clinical recovery scores, better quality-of-life scores, no serious adverse events linked to the cells, and weak MRI blood-flow findings.

Researchers’ Conclusions

• The researchers concluded that both IV and intrathecal UC-MSC treatment were linked with better recovery scores after ischemic stroke, with no serious adverse events considered related to the cells.
• IV looked like the better route overall because it had fewer adverse events, was less invasive, and showed strong clinical improvements.
• But this was still a small trial, so larger studies are needed before making stronger claims.
• Simple final takeaway:
• This trial found that UC-MSCs appeared safe and were linked with better functional recovery after ischemic stroke, but the MRI blood-flow results were not clearly positive.

Procedure

• Patients were randomly split into 3 groups:

Low-dose SB623 group:

• 2.5 million cells

Higher-dose SB623 group:

• 5 million cells

Control group:

• Sham surgery
• Each patient in the real treatment groups received SB623 cells implanted into the brain.

Delivery Method

• The treatment was delivered by stereotactic intracranial injection.
• That means a guided brain-surgery procedure was used to place the cells into the brain.
• The cells were implanted directly into brain tissue near the stroke-damaged area.

Cells Used

• The therapy used SB623 cells. These are modified donor-derived bone-marrow mesenchymal stem cells.
• The cells were temporarily altered in the lab so they could release repair-supporting signals after being implanted near the stroke-damaged area. (Notch-1 Pathway)

Follow-up Duration

• Patients were followed for the main outcome at 6 months.

Primary Outcome: Fugl-Meyer Motor Scale

• The main result measured whether patients had a meaningful improvement in movement after stroke, using a 0–100 motor score called the Fugl-Meyer Motor Scale.

Main Result

• The study did not meet its primary endpoint.
• The SB623 groups did not show a statistically significant improvement compared with sham surgery.
• When all patients were analysed together, SB623 did not clearly work better than sham surgery on the main movement score.

Secondary Measures

• The study also looked at:
• Modified Rankin Scale
• Action Research Arm Test
• Gait velocity
• NeuroQOL quality-of-life scores
• Global Rating of Perceived Change
• These measured things like disability, arm function, walking speed, quality of life, and whether the patient or clinician felt the patient had improved.
• But the headline result remained that the study failed its main endpoint.

Additional Analysis

• After the main trial failed, SanBio looked again at a smaller group of patients with smaller stroke-damaged areas.
• In this group:
• SB623 group: 49% improved
• Sham surgery group: 19% improved
• This suggests SB623 may work better for certain stroke patients, but because this was a later analysis, it is not as strong as the original main result.

Safety

• SB623 appeared safe in this trial, with no major safety issues reported.

Researchers’ Conclusions

• The original result was that the trial did not meet its main endpoint.
• SB623 looked safe, but the full Phase 2b stroke trial failed its main endpoint. A later analysis suggested it may help a more specific group of stroke patients, especially those with smaller areas of brain damage.
• Based on their later analysis, SanBio said it planned to prepare further late-stage trials for ischemic stroke and hemorrhagic stroke in Japan.

Procedure

• Patients were split into 2 groups:

Cord blood group:

• A single IV infusion of unrelated donor umbilical cord blood.

Placebo group:

• A single IV infusion of a placebo solution.
• The treatment was given through a peripheral IV line, meaning a normal IV line into a vein.

Cells Used

• The therapy used unrelated donor umbilical cord blood cells.
• These were donor cells from a public cord blood bank.
• They were selected based on:
• Blood type
• Race
• Target cell dose
• The dose was based on total nucleated cell count, or TNCC.
• The target dose was:
• 5 to 50 million total nucleated cells per kg body weight.

Cell Prep

• The cord blood units came from accredited US public cord blood banks.
• The units were:
• Selected
• Shipped frozen if needed
• Thawed
• Washed
• Tested
• Released
• Infused intravenously using standard operating procedures across the study sites

Follow-up Duration

• Patients were assessed after treatment at:
• 24 hours
• 30 days
• 90 days
• 180 days
• 365 days
• The main endpoint was measured at 3 months / 90 days.

Primary Outcome: mRS Disability Score

• The study wanted to know whether cord blood helped people recover more independence after a stroke.
• They measured this using a stroke disability score called the modified Rankin Scale, or mRS.
• A lower mRS score means the person is more independent.
• A higher mRS score means the person has more disability.
• After 3 months, both groups improved by the same amount on average.
• Cord blood group: 47 people were analysed, and the typical improvement was 1 point.
• Placebo group: 26 people were analysed, and the typical improvement was also 1 point.
• The difference was not statistically significant.
• That means the study did not show that cord blood helped people recover better than placebo.
• The main p-value was 0.71, and the adjusted p-value was 0.87, so neither analysis showed a clear benefit.

Functional Independence

• Functional independence meant the person had an mRS score of 0, 1, or 2 at 90 days.
• That means they were either symptom-free, had minor symptoms, or had mild disability but were still mostly independent.
• At 90 days:
• Cord blood group:
• 15 out of 47 people, or 31.9%, were functionally independent.
• Placebo group:
• 6 out of 26 people, or 23.1%, were functionally independent.
• This looks numerically better for cord blood, but the main trial result still did not prove a statistically significant benefit.

NIH Stroke Scale

• NIHSS = National Institutes of Health Stroke Scale.
• This measures stroke-related neurological problems.
• Higher scores mean worse impairment.
• At 90 days:
• Cord blood group:
• Median NIHSS score: 6
• Placebo group:
• Median NIHSS score: 6
• So on this measure, the groups looked very similar.

Barthel Index

• Barthel Index measures basic daily function, like mobility, feeding, dressing and using the bathroom.
• Higher scores mean more independence.
• At 90 days:
• Cord blood group:
• Median score: 80
• Placebo group:
• Median score: 85
• So the placebo group was slightly higher on this daily-function score, but this does not mean placebo was proven better. It just shows cord blood did not clearly outperform placebo here.

Quality of Life and Cognition

• The study also looked at:
• Stroke Impact Scale
• EQ-5D quality-of-life score
• PHQ-8 depression score
• Telephone Interview for Cognitive Status
• Trail Making Test
• MoCA cognitive score
• Hopkins Verbal Learning Test
• SF-36 health survey
• Controlled Oral Word Association Test
• Oral Symbol Digit Modalities Test
• These were secondary outcomes, meaning they were additional measures, not the main test of whether the treatment worked.

Safety

• The treatment did not show major product-specific safety problems.
• The safety results do not show obvious immune rejection problems like graft-versus-host disease, but this does not mean the treatment was effective.
• It means the treatment appeared reasonably tolerable in this trial, while the effectiveness result was negative or neutral.

Researchers’ Conclusions

• The researchers believed umbilical cord blood cells might help stroke recovery by reducing inflammation and supporting neuroprotection and brain plasticity.
• But the Phase 2 trial did not prove that this led to better recovery than placebo.

Procedure

• Patients were randomly split into 2 groups:

MSC group

• Patients received IV autologous MSC treatment.

Control group

• Patients received standard treatment only.

Delivery Method

• The treatment was given through an intravenous infusion.

Cells Used

• The therapy used:
• Autologous mesenchymal stem cells derived from Bone Marrow
• The study specifically used serum taken early after the stroke, described as autologous “ischemic” serum.
• The idea was to precondition the MSCs so they might have stronger repair/signaling effects.

Follow-up Duration

• The main result was measured at 90 days / 3 months after treatment.

Primary Outcome: mRS at 3 Months

• The main outcome was the modified Rankin Scale, or mRS.
• This measures how disabled or independent someone is after a stroke.

What they found

• The MSC group did not do significantly better than the control group on the main mRS outcome.
• The result was:
• p = 0.732
• That means the difference was not statistically significant.
• So the treatment did not clearly improve overall stroke recovery compared with standard treatment.

Secondary Outcomes

• The researchers looked at more detailed recovery measures.
• They found a possible benefit in lower limb / leg motor recovery.
• The MSC group improved more on the leg score of the Motricity Index.
• Result:
• p = 0.023
• This was especially noticeable in patients who were predicted to have low recovery potential.
• So in simple English:
• The treatment did not clearly improve overall disability, but it may have helped leg movement recovery in some patients.

Safety

• The treatment appeared feasible and safe in this study.
• The paper reported:
• No serious treatment-related adverse events
• The study also monitored risks like:
• Death
• Recurrent stroke or TIA
• Allergic reactions
• Infection
• Bone marrow aspiration complications
• Vascular obstruction
• Tumor formation
• Seizures
• Arrhythmia

Researchers’ Conclusions

• The researchers concluded that:
• IV autologous MSC treatment was feasible and appeared safe in patients with major ischemic stroke.
• But:
• It did not improve the main 90-day mRS outcome.
• They did observe:
• Some improvement in leg motor recovery on detailed functional testing.
• This study did not prove that the stem cells improved overall stroke recovery, but it did show the treatment looked safe and there was a possible signal for better leg movement recovery.

Procedure

• Patients were randomly split into 2 groups:

MultiStem / HLCM051 group

• Patients received one IV infusion of 1.2 billion HLCM051 cells.

Placebo group

• Patients received one IV infusion of placebo.
• The treatment was given 18 to 36 hours after ischemic stroke onset.

Delivery Method

• The treatment was given through an intravenous infusion.
• That means it was delivered into the bloodstream through an IV, not injected directly into the brain.

Cells Used

• The therapy used MultiStem / HLCM051, a manufactured product described as:
• Bone marrow–derived, allogeneic, multipotent adult progenitor cell product.
• In simple English:
• Bone marrow–derived = the original cell source comes from bone marrow.
• Allogeneic = the cells come from a donor, not from the patient.
• Multipotent adult progenitor cells = a specific adult progenitor cell product, not ordinary bone marrow MSC therapy.
• Off-the-shelf = the cells are manufactured in advance and can be used early after stroke.

Follow-up Duration

• Patients were followed up to 365 days.
• The main result was measured at Day 90.

Primary Outcome: Excellent Outcome at Day 90

• The main outcome was whether patients achieved an excellent recovery at Day 90.
• To count as an excellent outcome, patients had to meet all 3:
• mRS ≤ 1
• NIHSS ≤ 1
• Barthel Index ≥ 95

What they found

• At 90 days, 12 out of 104 patients who received MultiStem/HLCM051 had an excellent recovery, which equals 11.5%.
• In the placebo group, 10 out of 102 patients had an excellent recovery, which equals 9.8%.
• The result was not statistically significant, not enough people in the treatment group had an excellent recovery.
• So the treatment did not clearly improve recovery compared with placebo.

Secondary Outcomes

• The paper says there were no between-group differences in primary and secondary endpoints.
• That means the broader recovery measures also did not show a clear advantage for MultiStem over placebo in this trial.

Safety

• The treatment appeared safe in this study.
• The paper reported:
• Adverse events were similar between the MultiStem and placebo groups.
• There were no grade 3 or 4 allergic reactions.
• The results supported the safety of MultiStem, including in older patients.

Researchers conclusions

• The researchers concluded that:
• MultiStem / HLCM051 was safe when given by IV within 18 to 36 hours after ischemic stroke.
• It did not improve short-term outcomes compared with placebo.
• There were no significant differences between MultiStem and placebo for the main recovery outcomes.
• More research is needed to see whether it could help a specific subgroup of patients.

Procedure

• Patients were randomly split into 3 groups:

Control group:

• Standard medical stroke care only.

Low-dose BMMNC group:

• 2 million bone marrow mononuclear cells per kg of body weight.

High-dose BMMNC group:

• 5 million bone marrow mononuclear cells per kg of body weight.
• Each patient in the treatment groups received one intra-arterial injection of their own bone marrow cells.

Delivery Method

• The treatment was given intra-arterially.
• That means the cells were injected into an artery, not into a normal IV vein drip.

Cells Used

• The study used autologous bone marrow mononuclear cells, also called BMMNCs.
• Autologous means the cells came from the same patient.
• Bone marrow mononuclear cells are a mixed group of cells taken from bone marrow. They are not one purified stem cell type.
• These cells were not culture-expanded.

Follow-up Duration

• Patients were followed for 24 months.
• The main outcome was measured at 6 months / 180 days.

Primary Outcome: Modified Rankin Scale

• The main outcome was the percentage of patients with a modified Rankin Scale score of 0–2 at 6 months.
• Modified Rankin Scale, or mRS, measures disability after stroke.

Simple version:

• 0 = no symptoms
• 1 = symptoms but no major disability
• 2 = slight disability, but still independent
• 3–5 = increasing levels of disability
• 6 = death
• So an mRS score of 0–2 means the person is independent or close to independent.

Main Result at 6 Months

• At 6 months:
• Control group: 14 out of 36 patients, or 39%, reached mRS 0–2.
• Low-dose group: 10 out of 20 patients, or 50%, reached mRS 0–2.
• High-dose group: 8 out of 18 patients, or 44%, reached mRS 0–2.
• Pooled BMMNC group: 18 out of 38 patients, or 47%, reached mRS 0–2.
• The cell treatment groups looked slightly better numerically, but the difference was not statistically significant.
• So the simple conclusion is:
• The treatment did not clearly improve stroke recovery at 6 months compared with standard care.

NIHSS and Barthel

• The study also looked at:
• NIHSS
• Barthel Index
• NIHSS measures stroke severity.
• Barthel measures independence with daily activities.
• These were secondary/other functional outcomes.

MRI / Infarct Volume

• The study also looked at changes in infarct volume on MRI between baseline and 6 months.
• Infarct volume means the size of the damaged brain area after the stroke.
• Did not show a clear meaningful MRI regeneration result, so this should not be described as brain tissue regeneration.

Safety

• The treatment appeared safe overall.
• The study found no major difference in adverse events between groups.
• There was no clear dose-related safety problem.
• However, two patients in the low-dose group had a groin haematoma after cell injection.
• A groin haematoma means bleeding/bruising at the catheter access site, likely because the artery was accessed through the groin.

Mortality

• Mortality was tracked for 24 months.

Researchers conclusions

• The researchers concluded that:
• Intra-arterial autologous bone marrow mononuclear cell treatment was safe in patients with acute ischemic stroke.
• But the treatment did not produce a statistically significant improvement in the main 6-month recovery outcome.
• They said more studies are needed to see whether benefits might be possible at different timepoints or with different trial designs.

Procedure

• Patients were randomly split into 2 groups:
• Stem cell group: received allogeneic adipose-derived MSCs.
• Placebo group: received a placebo IV solution.
• The treatment was given as one single IV infusion.
• The cells were given within the first 2 weeks after stroke symptoms started.

Delivery Method

• The cells were given intravenously.

Cells Used

• The study used: Allogeneic adipose-derived mesenchymal stem cells

Dosage:

• The dose was:
• 1 million AD-MSCs per kg of body weight
• So for example:
• A 70 kg patient would receive about 70 million cells total.

Follow-up Duration

• Patients were followed for 24 months.
• The main thing they were checking was safety.
• They also looked at whether the cells might improve stroke recovery.

Primary Outcome: Safety

• The main outcome was safety.
• They looked for:
• Adverse events.
• Serious adverse events.
• Neurological complications.
• Systemic complications.
• Tumor development.
• Stroke worsening.
• Stroke recurrence.
• Brain swelling.
• Seizures.
• Bleeding transformation.
• Respiratory infections.
• Urinary tract infections.
• Deep vein thrombosis.
• Pulmonary embolism.
• Gastrointestinal bleeding.

Safety Results

• Across 24 months, there were 124 adverse events in total.
• 50 happened in the AD-MSC group.
• 74 happened in the placebo group.
• There were 11 serious adverse events:
• 2 in the stem cell group.
• 9 in the placebo group.
• Importantly:
• No adverse event was considered related to the stem cell treatment.
• No infusion-related adverse events were reported.
• No tumors were reported.
• One patient died, but this was in the placebo group, not the stem cell group.

Stroke Recovery: mRS Score

• mRS means Modified Rankin Scale. It measures how disabled or independent someone is after a stroke.
• Lower score = better function.
• The study found:
• No significant difference between the stem cell group and placebo group in mRS scores.
• So they could not prove the cells improved overall disability.

Stroke Severity: NIHSS Score

• NIHSS means National Institutes of Health Stroke Scale. It measures stroke symptoms and neurological deficit.
• Lower score = better.
• At 24 months:
• Stem cell group median NIHSS: 3
• Placebo group median NIHSS: 7
• That looks better for the stem cell group, but it was not statistically significant. So this is only a weak signal, not proof.

MRI / Infarct Size

• They also looked at infarct size on MRI. Infarct size means the amount of brain tissue damaged by the stroke.
• The study found:
• No significant difference in infarct size between groups.

Blood Biomarkers

• They checked blood markers linked to brain repair and inflammation, including:
• BDNF.
• VEGF.
• MMP-9.
• Extracellular vesicles.
• They did not find clear useful differences showing that the stem cells caused better biological repair.
• Some biomarker patterns were different, but the researchers said the small sample size makes this hard to trust.

Researchers conclusions

• The researchers concluded that:
• IV allogeneic adipose-derived MSCs were safe and well tolerated.
• But they also concluded that:
• The study was too small to prove effectiveness and no efficacy endpoint was statistically significant.
• There was only a possible trend toward better NIHSS scores in the stem cell group.
• The researchers then used this safety data to support the next study, AMASCIS-02, which tests giving the treatment earlier after stroke

Procedure

• Patients were randomly split into 2 groups:

CL2020 group:

• Received CL2020 Muse cells

Placebo group:

• Received placebo without cells
• Each patient received one treatment only.

Delivery Method

• The treatment was given intravenously over 10–15 minutes.
• The CL2020 product was thawed, diluted, and then infused into the patient.
• All patients also continued with a standard rehabilitation program.

Cells Used

• The therapy used CL2020, which is an allogeneic Muse cell-based product.
• Allogeneic means the cells came from a donor, not from the patient.
• The dose was: 15 million cells.

Muse Cells vs MSC Cells

• This is important.
• MSCs are mesenchymal stem/stromal cells.
• They are commonly used in many stem cell trials.
• In simple terms, MSCs mainly seem to work by releasing helpful signals. These signals may calm inflammation and support repair.
• But in stroke, standard MSCs have a problem:
• After IV infusion, many cells may get trapped in the lungs and may not reach the damaged brain area well.
• The paper says previous stem cell studies may have had limited results partly because of poor homing to the stroke-damaged area.
• Muse cells are different.
• Muse cells are described as a special subpopulation found within broader cell populations like MSCs.
• The paper says Muse cells can:
• Detect damaged tissue
• Move toward injury signals
• Travel to damaged tissue after IV injection
• Potentially differentiate into the right cell types
• Potentially avoid strong immune rejection
• The authors say Muse cells can detect an injury signal called sphingosine-1-phosphate.
• That may help them travel to damaged tissue instead of mainly getting stuck in the lungs.
• So simply:
• MSCs = broad repair-signalling cells.
• Muse cells = a selected cell type claimed to have better injury-homing and more ability to become replacement cells.
• Important:
• This human study did not directly prove that the Muse cells became brain cells inside patients.
• The stronger evidence for homing and differentiation comes from earlier animal studies.

Follow-up Duration

• Patients were followed for 52 weeks.
• The main safety endpoint was at 12 weeks.
• The main efficacy result was also measured at 12 weeks.

Primary Outcome: Safety

• Safety was the main endpoint.
• By week 12:
• CL2020 group:
• 24 out of 25 patients had adverse events.
• Placebo group:
• 10 out of 10 patients had adverse events.
• Most adverse events were things like gastrointestinal issues, infections, pain, insomnia, headache, skin changes, or other medical problems that can happen in this type of stroke population.
• By week 12:
• Adverse reactions possibly related to treatment:
• CL2020: 7 out of 25 patients
• Placebo: 1 out of 10 patients
• There was one serious adverse reaction in the CL2020 group:
• A 56-year-old man had Grade 4 status epilepticus 86 days after CL2020 treatment.
• He recovered, but the researchers said the relationship to CL2020 could not be ruled out.
• By week 52:
• All patients in both groups had at least one adverse event.
• Serious adverse events occurred in:
• CL2020: 5 patients
• Placebo: 1 patient
• The authors concluded there were no major safety issues, but the seizure event is important to mention.

Main Recovery Result: mRS Score

• mRS means modified Rankin Scale. It measures disability after stroke.
• The main recovery question was:
• How many patients reached mRS 0–2 by week 12?
• At 12 weeks:
• CL2020 group:
• 10 out of 25 patients reached mRS 0–2
• That equals 40%
• Placebo group:
• 1 out of 10 patients reached mRS 0–2
• That equals 10%
• CL2020 looked better than placebo, but the study did not statistically prove the main result.

Important Detail: Study’s Own Success Threshold

• The study also compared the CL2020 group against a pre-set benchmark from registry data.
• That benchmark was 8.7%.
• The CL2020 group’s result was 40%, and the lower confidence interval was above that benchmark.
• So by the study’s own design, the result was considered promising.
• But compared directly against placebo, it did not reach standard statistical significance.

Motor Function: Fugl-Meyer Motor Scale

• The Fugl-Meyer Motor Scale measures movement recovery after stroke.
• The CL2020 group showed stronger improvement in:
• Upper limb movement
• Total motor score
• This means the treated group seemed to have better arm and overall movement recovery.
• Lower limb improvement was not clearly better than placebo.

Other Stroke Scores

• The researchers also looked at:
• NIHSS
• SIAS
• Barthel Index
• EQ-5D quality of life
• VAS quality-of-life score
• Some results looked better in the CL2020 group, but not all were clearly different from placebo.
• Quality of life improved more in the CL2020 group at week 12.

Safety

• The treatment was generally described as having no major safety issues, but it was not completely clean.
• Important safety findings:
• Most patients in both groups had adverse events.
• One CL2020 patient had a serious adverse reaction: Grade 4 status epilepticus.
• Some CL2020 patients had hair color changes from gray/white to black.
• There were no adverse reactions leading to death or treatment discontinuation.
• The authors said the seizure event was not considered unusual in a post-stroke population, but the relationship to CL2020 could not be ruled out.
• Simple safety sentence:
• CL2020 appeared generally tolerable in this small study, but one serious seizure-related event occurred and may have been related to treatment.

How the Cells Were Supposed to Work

• The researchers believe Muse cells may help stroke recovery differently from ordinary MSCs.
• 1. Better Homing to Damaged Tissue
• The authors say Muse cells can detect injury signals and travel to damaged tissue after IV infusion.
• This is important because many standard stem cells given by IV may get trapped in the lungs instead of reaching the injured brain area.
• 2. Possible Differentiation Into Brain-Related Cells
• In animal stroke studies, Muse cells were reported to become neuronal and glial cells.
• Neuronal cells are nerve-related cells.
• Glial cells are support cells in the nervous system.
• The authors believe this could help repair damaged brain tissue.
• Important:
• This human study did not directly prove that CL2020 cells became new brain cells in patients.
• It measured patient recovery, not direct cell tracking inside the human brain.
• 3. Possible Neural Circuit Repair
• The animal studies suggested Muse cells may help rebuild damaged neural circuits.
• That means they may help restore communication pathways in the brain.
• But again, this was not directly proven in the human patients.
• 4. Immune Tolerance
• The paper says allogeneic Muse cells may be used without HLA matching or immunosuppressants.
• This may be partly because Muse cells express HLA-G, which is linked with immune tolerance.
• Simple mechanism:
• Muse cells are designed to travel to injured tissue, possibly become useful repair cells, and support recovery without needing immune-suppressing drugs.

Researchers Conclusions

• The researchers concluded that:
• CL2020 may be a safe and effective treatment for subacute ischemic stroke.
• Patients receiving CL2020 had a higher recovery response rate than placebo at 12 weeks.
• CL2020 showed promising improvements in motor function, especially upper limb movement.
• The study was exploratory and small.
• A larger Phase 3 trial would be needed to confirm the results.
• Important context: Mitsubishi Chemical Group later discontinued development of CL2020 in February according to their own press release.

Procedure

• Patients were randomly split into 2 groups:

CL2020 group:

• Received CL2020 Muse cells

Placebo group:

• Received placebo without cells
• Each patient received one treatment only.

Delivery Method

• The treatment was given intravenously over 10–15 minutes.
• The CL2020 product was thawed, diluted, and then infused into the patient.
• All patients also continued with a standard rehabilitation program.

Cells Used

• The therapy used CL2020, which is an allogeneic Muse cell-based product.
• Allogeneic means the cells came from a donor, not from the patient.
• The dose was: 15 million cells.

Muse Cells vs MSC Cells

• This is important.
• MSCs are mesenchymal stem/stromal cells.
• They are commonly used in many stem cell trials.
• In simple terms, MSCs mainly seem to work by releasing helpful signals. These signals may calm inflammation and support repair.
• But in stroke, standard MSCs have a problem:
• After IV infusion, many cells may get trapped in the lungs and may not reach the damaged brain area well.
• The paper says previous stem cell studies may have had limited results partly because of poor homing to the stroke-damaged area.
• Muse cells are different.
• Muse cells are described as a special subpopulation found within broader cell populations like MSCs.
• The paper says Muse cells can:
• Detect damaged tissue
• Move toward injury signals
• Travel to damaged tissue after IV injection
• Potentially differentiate into the right cell types
• Potentially avoid strong immune rejection
• The authors say Muse cells can detect an injury signal called sphingosine-1-phosphate.
• That may help them travel to damaged tissue instead of mainly getting stuck in the lungs.
• So simply:
• MSCs = broad repair-signalling cells.
• Muse cells = a selected cell type claimed to have better injury-homing and more ability to become replacement cells.
• Important:
• This human study did not directly prove that the Muse cells became brain cells inside patients.
• The stronger evidence for homing and differentiation comes from earlier animal studies.

Follow-up Duration

• Patients were followed for 52 weeks.
• The main safety endpoint was at 12 weeks.
• The main efficacy result was also measured at 12 weeks.

Primary Outcome: Safety

• Safety was the main endpoint.
• By week 12:
• CL2020 group:
• 24 out of 25 patients had adverse events.
• Placebo group:
• 10 out of 10 patients had adverse events.
• Most adverse events were things like gastrointestinal issues, infections, pain, insomnia, headache, skin changes, or other medical problems that can happen in this type of stroke population.
• By week 12:
• Adverse reactions possibly related to treatment:
• CL2020: 7 out of 25 patients
• Placebo: 1 out of 10 patients
• There was one serious adverse reaction in the CL2020 group:
• A 56-year-old man had Grade 4 status epilepticus 86 days after CL2020 treatment.
• He recovered, but the researchers said the relationship to CL2020 could not be ruled out.
• By week 52:
• All patients in both groups had at least one adverse event.
• Serious adverse events occurred in:
• CL2020: 5 patients
• Placebo: 1 patient
• The authors concluded there were no major safety issues, but the seizure event is important to mention.

Main Recovery Result: mRS Score

• mRS means modified Rankin Scale. It measures disability after stroke.
• The main recovery question was:
• How many patients reached mRS 0–2 by week 12?
• At 12 weeks:
• CL2020 group:
• 10 out of 25 patients reached mRS 0–2
• That equals 40%
• Placebo group:
• 1 out of 10 patients reached mRS 0–2
• That equals 10%
• CL2020 looked better than placebo, but the study did not statistically prove the main result.

Important Detail: Study’s Own Success Threshold

• The study also compared the CL2020 group against a pre-set benchmark from registry data.
• That benchmark was 8.7%.
• The CL2020 group’s result was 40%, and the lower confidence interval was above that benchmark.
• So by the study’s own design, the result was considered promising.
• But compared directly against placebo, it did not reach standard statistical significance.

Motor Function: Fugl-Meyer Motor Scale

• The Fugl-Meyer Motor Scale measures movement recovery after stroke.
• The CL2020 group showed stronger improvement in:
• Upper limb movement
• Total motor score
• This means the treated group seemed to have better arm and overall movement recovery.
• Lower limb improvement was not clearly better than placebo.

Other Stroke Scores

• The researchers also looked at:
• NIHSS
• SIAS
• Barthel Index
• EQ-5D quality of life
• VAS quality-of-life score
• Some results looked better in the CL2020 group, but not all were clearly different from placebo.
• Quality of life improved more in the CL2020 group at week 12.

Safety

• The treatment was generally described as having no major safety issues, but it was not completely clean.
• Important safety findings:
• Most patients in both groups had adverse events.
• One CL2020 patient had a serious adverse reaction: Grade 4 status epilepticus.
• Some CL2020 patients had hair color changes from gray/white to black.
• There were no adverse reactions leading to death or treatment discontinuation.
• The authors said the seizure event was not considered unusual in a post-stroke population, but the relationship to CL2020 could not be ruled out.
• Simple safety sentence:
• CL2020 appeared generally tolerable in this small study, but one serious seizure-related event occurred and may have been related to treatment.

How the Cells Were Supposed to Work

• The researchers believe Muse cells may help stroke recovery differently from ordinary MSCs.
• 1. Better Homing to Damaged Tissue
• The authors say Muse cells can detect injury signals and travel to damaged tissue after IV infusion.
• This is important because many standard stem cells given by IV may get trapped in the lungs instead of reaching the injured brain area.
• 2. Possible Differentiation Into Brain-Related Cells
• In animal stroke studies, Muse cells were reported to become neuronal and glial cells.
• Neuronal cells are nerve-related cells.
• Glial cells are support cells in the nervous system.
• The authors believe this could help repair damaged brain tissue.
• Important:
• This human study did not directly prove that CL2020 cells became new brain cells in patients.
• It measured patient recovery, not direct cell tracking inside the human brain.
• 3. Possible Neural Circuit Repair
• The animal studies suggested Muse cells may help rebuild damaged neural circuits.
• That means they may help restore communication pathways in the brain.
• But again, this was not directly proven in the human patients.
• 4. Immune Tolerance
• The paper says allogeneic Muse cells may be used without HLA matching or immunosuppressants.
• This may be partly because Muse cells express HLA-G, which is linked with immune tolerance.
• Simple mechanism:
• Muse cells are designed to travel to injured tissue, possibly become useful repair cells, and support recovery without needing immune-suppressing drugs.

Researchers Conclusions

• The researchers concluded that:
• CL2020 may be a safe and effective treatment for subacute ischemic stroke.
• Patients receiving CL2020 had a higher recovery response rate than placebo at 12 weeks.
• CL2020 showed promising improvements in motor function, especially upper limb movement.
• The study was exploratory and small.
• A larger Phase 3 trial would be needed to confirm the results.
• Important context: Mitsubishi Chemical Group later discontinued development of CL2020 in February according to their own press release.

What they’re trying to find out

• Whether MSC therapy could help people recover after stroke.
• Whether MSCs can:
• Reduce brain inflammation after stroke
• Protect damaged brain cells
• Support new blood vessel growth
• Support nerve repair and brain recovery
• Improve movement and function after stroke
• Reduce the size or effects of stroke-related brain damage
• Help the brain repair itself after injury
• They were also trying to understand whether MSCs work mainly by:
• Becoming new brain cells directly
• OR
• Sending out healing signals that calm inflammation and improve the repair environment.
• The review leans more toward the second explanation: MSCs likely help mostly through signaling and repair support, not simple tissue replacement.

1. Preclinical findings

• Preclinical studies suggest MSCs may help the brain recover after stroke, but this evidence mostly comes from lab and animal studies.
• The main finding was that MSCs may help by improving the damaged brain environment, rather than simply replacing dead brain cells.
• MSCs may do this by reducing inflammation, releasing healing signals and exosomes, protecting damaged brain cells, helping new blood vessels form, supporting nerve repair, and possibly helping damaged cells regain energy function.
• This is promising, but it does not prove MSCs work in human stroke patients yet.

2. Clinical findings

• The review found 27 registered clinical trials looking at MSCs or other stem-cell approaches for stroke.
• Overall, the human evidence is still early and mixed.
• Some studies reported that MSC treatment appeared safe and may have helped recovery in some patients.
• Other studies did not show a clear improvement compared with placebo or control groups.
• The trials were also difficult to compare because they used different cell sources, doses, timings, delivery methods, and patient groups.
• Clinical takeaway:
• MSC therapy for stroke has shown some promising safety and recovery signals, but the evidence is not strong enough yet to say it is a proven treatment. Larger, better-controlled trials are still needed.

3. Stem cell source comparison

• The review does not show that one MSC source is clearly the best for stroke.
• Bone marrow and umbilical cord MSCs are the main sources being tested in human stroke trials, but the studies are too different to directly compare.
• The practical issue is that a patient’s own cells may be safer from an immune-matching perspective, but they take time to collect and prepare, which is a problem after an acute stroke.
• Donor cells, especially umbilical cord-derived MSCs, may be more practical because they can be prepared in advance, but their long-term effectiveness still needs more evidence.
• Main takeaway:
• There is no proven “best” stem cell source for stroke yet. The best option may depend on timing, safety, cell quality, and whether the treatment needs to be ready quickly after the stroke.

4. Safety

• The review suggests MSC therapy appears generally safe in the studies discussed, but the evidence is still limited.
• Some trials reported no serious adverse events.
• However, the researchers do not say the safety question is fully settled. They explain that more research is still needed because studies used different cell sources, doses, delivery methods, and patient groups.

5. Limitations across trials

• The researchers repeatedly point out that the evidence is hard to compare because studies are very different.
• Main limitations:
• Small patient numbers
• Many studies are early phase
• Different stem cell sources used
• Different doses used
• Different delivery routes used
• Different timing after stroke
• Different stroke types and severities
• Different outcome measures
• Some studies had no placebo group
• Some were not designed to prove effectiveness
• The review also says the best timing for MSC treatment is still unclear. Many preclinical studies suggest earlier treatment may be better, possibly within 48 hours after acute stroke, but this is hard to do with the patient’s own cells because preparing autologous MSCs takes time.

What they concluded

• MSC therapy for stroke is promising but still investigational.
• The researchers believe MSCs may help through:
• Reducing inflammation
• Sending healing signals
• Supporting new blood vessel growth
• Protecting damaged brain cells
• Supporting nerve repair
• Improving the brain’s healing environment
• They do not conclude that MSCs are already a proven stroke treatment.
• They say the field still needs:
• Larger randomized controlled trials
• Longer follow-up
• Standardized treatment protocols
• Better comparison between cell sources
• Clearer dosing guidance
• Better understanding of the best timing
• Better understanding of the best delivery route
• MSC therapy may become useful for stroke recovery in the future, but right now the evidence is still early. Preclinical evidence is promising, and some clinical studies suggest safety and possible benefit, but results are mixed and not strong enough yet to call it an established treatment.

What they’re trying to find out

• Whether stem cell therapy is effective for people who have had an ischemic stroke.

The main recovery measures were:

• mRS — Modified Rankin Scale
• This measures disability after stroke.
• Barthel Index
• This measures how well someone can do daily activities.
• NIHSS — National Institutes of Health Stroke Scale
• This measures neurological problems after stroke.

The safety measures included:

• death
• adverse events
• infection
• seizures
• recurrent stroke or TIA
• bleeding in the brain
• neurological worsening
• tumour formation

1. Effectiveness

• Stem cell therapy was linked with better mRS scores. This means patients in the stem cell group had better disability outcomes than the control group.
• Stem cell therapy was also linked with better Barthel Index scores. This means patients in the stem cell group had better daily function than the control group.
• Stem cell therapy was linked with lower mortality. This means fewer patients died in the stem cell group compared with the control group.
• But stem cell therapy did not significantly improve NIHSS scores.
• So, the researchers found improvement in some functional recovery measures, but not a clear improvement in neurological impairment scores.

2. Mechanism of action

• The researchers said the exact way stem cells may help after ischemic stroke is still not fully understood.
• Earlier ideas suggested stem cells might replace lost neurons.
• But the researchers said newer evidence suggests stem cells mainly work by releasing helpful signals.
• These signals may:
• reduce inflammation
• support neurogenesis — the growth or repair of nerve cells
• support angiogenesis — new blood vessel growth
• help brain recovery after stroke
• So, in simple terms:
• The researchers do not suggest stem cells are mainly working by directly replacing dead brain tissue.
• They suggest they may work more by sending repair and anti-inflammatory signals that help the damaged brain environment recover.

3. Stem cell source comparison

• Autologous stem cells, patient’s own cells:
• The subgroup analysis found autologous stem cell therapy was linked with significant improvements in:
• mRS
• Barthel Index
• That means the patient’s own cells were linked with better disability and daily function outcomes.
• Allogeneic stem cells:
• The subgroup analysis found allogeneic stem cell therapy was linked with significant improvement in:
• NIHSS. That means donor cells were linked with better neurological impairment scores.
• However, the researchers did not say one cell type is definitely best.
• They said the results may be affected by differences in study design, cell type, delivery route, timing, and number of trials.

4. Delivery route and timing

• The researchers split results by how the cells were delivered.
• Routes included:
• intravenous — through a vein
• intra-arterial — through an artery
• intrathecal / lumbar subarachnoid — into the spinal fluid area
• intracerebral — directly into the brain
• They found:
• Intrathecal delivery was linked with better mRS and Barthel Index scores.
• Intracerebral delivery was linked with better mRS and NIHSS scores.
• The researchers said targeted delivery methods may work better because they may get more cells closer to the damaged area.
• But they also said targeted methods are harder to use in normal clinical practice.
• They also found:
• subacute treatment improved Barthel Index
• acute and chronic treatment improved NIHSS
• Subacute means 8 days to 3 months after stroke.
• Acute means up to 7 days after stroke.
• Chronic means more than 3 months after stroke.

5. Cell culture and preparation insights

• The trials used many different cell products, sources, doses, and delivery methods.
• The researchers said these differences make it hard to determine the best:
• cell type
• dose
• delivery route
• treatment timing
• They also said stem cell therapy requires specialist culture facilities, strict transport systems, and standardised manufacturing to make sure the treatment is consistent and controlled.

6. Safety

• The researchers found no major increase in adverse events in the stem cell group compared with the control group.
• They reported no cases of:
• tumour formation in the stroke lesion
• severe neurological worsening without recurrent stroke
• They also found no significant difference between stem cell and control groups for:
• infections
• symptomatic brain bleeding
• recurrent stroke or TIA
• seizures
• Mortality was lower in the stem cell therapy group.

7. Limitations across trials

• The researchers said the evidence is still limited because:
• the studies were very different from each other
• cell types varied
• doses varied
• delivery routes varied
• treatment timing varied
• follow-up periods varied
• some studies had small sample sizes
• many studies had moderate risk of bias
• some data was missing because authors did not respond to data requests
• They also said the positive disability findings were fragile.
• This means the result looked positive overall, but when certain studies were removed from the analysis, the benefit was no longer clearly significant.
• Because of this, the researchers said firm conclusions cannot be made yet.

What they concluded

• Stem cell therapy shows promise for ischemic stroke.
• The researchers concluded that stem cell therapy may improve:
• functional recovery
• daily activity ability
• survival after stroke
• They did not find major safety concerns in the trials reviewed.
• However, they said stem cell therapy is not ready for routine clinical use yet.
• The reasons were:
• trial results were inconsistent
• study quality was moderate
• cell types were different
• doses were different
• delivery routes were different
• the strongest disability findings were fragile
• the best cell type, dose, and delivery method are still not known
• The researchers said larger, high-quality phase III randomized controlled trials are still needed to confirm safety and effectiveness and to work out the best treatment protocol.

What they’re trying to find out

• Whether brain imaging can show useful signs that stem cell therapy is helping after ischemic stroke.
• They wanted to know whether brain scans could show signs that stem cells were helping after a stroke.
• They looked for things like:
• Whether the damaged area got smaller
• Whether the brain pathways looked healthier
• Whether brain activity improved
• Whether blood flow and energy use improved
• Whether the cells moved toward the injured area
• Whether the area around the stroke injury showed signs of repair

1. Stroke scar / infarct size

• Stem cell therapy did not clearly reduce the size of the stroke-damaged area.
• In subacute stroke patients, there was no significant difference in infarct volume reduction at:
• 3 months
• 1 year
• So, the dead stroke area did not clearly shrink compared with control groups.
• The researchers said infarct volume may be an insensitive marker for stem cell therapy because repair may happen around the damaged area instead of inside the dead core.

2. White matter / nerve pathway changes

• Some DTI studies showed possible improvement or preservation of white matter pathways.
• The main pathway discussed was the corticospinal tract, which is important for movement.
• Some studies reported better DTI measures after treatment, including changes in FA, relative FA, and fiber number measures.
• The researchers said these findings may suggest better preservation or recovery of movement-related brain pathways, but the changes were small and the imaging methods differed between studies.

3. Brain activity changes

• Some fMRI studies showed increased activity in motor areas of the brain after stem cell therapy.
• This included increased activation in the primary motor cortex, an area involved in movement.
• The researchers said this may suggest brain network reorganization or neuroplasticity after treatment.

4. Blood flow and metabolism

• PET and perfusion imaging showed possible improvements in blood flow and metabolism around the stroke area.
• The researchers were especially interested in the peri-infarct region, meaning the surviving tissue around the stroke injury.
• They suggested this surrounding area may be important because it may still be alive and able to support repair.

5. Cell tracking / migration

• One study used SPIO-labelled autologous bone marrow-derived stromal cells so the cells could be followed on MRI.
• The labelled cells were first seen near the injection site.
• Later, new MRI signals appeared near the stroke area between 1 and 6 months.
• These signals persisted for at least 1 year.
• The researchers interpreted this as possible cell migration and persistence near the injured area.
• Simple wording:
• The cells appeared to move toward the injured stroke area, which may suggest homing, but the imaging does not prove that all cells were alive for 1 year.

6. Safety

• The review said clinical trials to date have demonstrated safety and feasibility.
• For the SPIO-labelled cell tracking study, the researchers said labelled autologous stem cells recently proved safe in patients.
• The review also mentioned reported complications from other reviews, including subdural hematoma, epidural hematoma, and brain bleeding, but this was discussed as something radiologists should be aware of when interpreting scans after treatment.

7. Limitations across trials

• The researchers said the evidence is limited because:
• Studies were small
• Many studies were early-phase trials
• Many studies did not have strong control groups
• Some studies had serious risk of bias
• Imaging methods were not standardized
• Different studies used different cell types
• Different studies used different delivery routes
• Different studies used different doses and follow-up times
• It was not possible to properly compare IV vs direct brain injection because the studies were too different.

What they concluded

• Stem cell therapy for ischemic stroke did not clearly make the stroke scar smaller on MRI.
• However, advanced brain imaging showed possible signs of repair in the surviving tissue and brain networks around the stroke injury.
• The researchers said the most useful imaging markers may be things like:
• White matter pathway changes
• Motor cortex activity
• Brain network changes
• Blood flow
• Metabolism
• Peri-infarct region changes
• Cell tracking
• They concluded that neuroimaging is useful for understanding how stem cell therapy may affect the injured brain.
• However, they said larger, better-controlled studies with standardized imaging methods are needed before stronger conclusions can be made