Stem Cell Research: MS

Delivery Method

Intravenous (IV) chemotherapy is given to prepare the body, followed by a single IV reinfusion of the patient’s own stem cells.

Cell Dosage

Patients receive a minimum of 3.0 million cells per kilogram of body weight.

Cell Type Used

Autologous Hematopoietic Stem Cells (HSCT): These are the patient’s own blood-forming stem cells, collected from their bloodstream.

Follow-up

Participants will be monitored for a 7-year period.

Primary Outcome

The main goal is to measure the proportion of patients with No Evidence of Disease Activity. This is defined as having no MS relapses, no new MRI lesions & no worsening of disability over two years.

Secondary Outcomes

Researchers will also track many other measures, including:

• Time to a first relapse
• Changes in brain volume (atrophy)
• Changes in disability scores (EDSS)
• Performance on physical tasks like the Timed 25 Foot Walk

Delivery Method

A high-dose chemotherapy “conditioning” regimen is given, followed by a single IV infusion of the patient’s own thawed stem cells.

Cell Preparation

The process does not involve culturing cells. It follows three main steps:

• Mobilization: The patient is given medications to move the stem cells from the bone marrow into the bloodstream.
• Collection: The stem cells are then collected from the blood using a procedure called leukapheresis.
• Storage: The collected cells are frozen until they are needed for the infusion.

Cell Dosage

The target dose for infusion is 5 million cells per kilogram of body weight. Minimum allowed dose: 4 million; Maximum: 7.5 million cells/kg.

Cell Type Used

Autologous Hematopoietic Stem Cells (AHSCT): These are the patient’s own blood-forming stem cells collected from their peripheral blood.

Follow-up

Participants will be monitored for a total of 6 years after they are randomized into a treatment group.

Primary Outcome

The main goal is to measure MS relapse-free survival. This is defined as the length of time a patient goes without having an MS relapse or dying from any cause.

Secondary Outcomes

Researchers will also track many other measures, including:

• Annual number of relapses
• Any worsening or improvement of disability on the EDSS scale
• Changes in whole brain volume on MRI
• Levels of a nerve damage biomarker in the blood

Delivery Method

Each patient will receive six IV infusions of stem cells, given over a period of 32 weeks.

Cell Type & Source

Autologous adipose-derived mesenchymal stem cells.
Source: The patient’s own fat tissue.
The cells are autologous, which means they come from the patient’s own body.

Cell Preparation

They only state that participants must have previously banked their stem cells with Hope Biosciences.

Since there are no results yet, this section outlines what the study is designed to measure.

Safety

Researchers will closely monitor the incidence of all adverse events to continue evaluating the treatment’s safety profile.

Primary Outcome

The main goal is to measure the change in patients’ quality of life over one year, using the MSQOL-54 questionnaire.

Secondary Outcomes

Researchers will also track changes in the EDSS disability score and symptoms of depression (using the PHQ-9 score) to see if the positive results from the first trial are repeated in this group.

Delivery Method

Each patient received six intrathecal injections into the spinal fluid, spaced two months apart over one year.

Cell Type & Source

Autologous Mesenchymal Stem Cell-Neural Progenitors (MSC-NPs).
Source: The patient’s own bone marrow.
These cells are created when standard bone marrow MSCs are “reprogrammed” in a lab. They are cultured for two weeks in “neural maintenance media” that enriches them with genes related to the nervous system, making them more specialized.

Cell Preparation

MSCs were isolated from bone marrow and expanded in the lab.
The cells were frozen at passages 2 and 3. Before each treatment, they were thawed and expanded for 2 more passages before being turned into MSC-NPs.

Dosage

Each injection contained a dose of up to 10 million cells.

Safety

The treatment was safe and well-tolerated. No serious adverse events were found to be related to the stem cell injections. The most common related side effect was a temporary headache after the procedure.

Clinical Improvements (Primary Outcome)

The study failed to meet its primary endpoint, EDSS Plus.
There was no statistical difference in improvement between the stem cell group (33% of patients improved) and the placebo group (37% of patients improved).

Other Key Findings (Secondary Outcomes)

• Improved Walking: In a subgroup of patients with more advanced disability who needed walking aids (EDSS 6.0-6.5), the stem cell treatment led to significantly better walking speed and endurance compared to the placebo group.
• Improved Bladder Function: The treatment was associated with significantly improved bladder function. 76% of patients showed better bladder emptying after receiving stem cells, compared to only 27% in the placebo group.
• Neuroprotection: The therapy appeared to slow the rate of grey matter atrophy (loss of brain tissue) in a subgroup of patients, suggesting a neuroprotective effect.

How the Cells Worked

The researchers believe the MSC-NPs worked by helping the nervous system, not by replacing damaged tissue.
The cells did not turn into new nerve cells.
Instead, they worked through paracrine signaling, releasing helpful substances which calm inflammation and support existing cells.
This was supported by changes in specific biomarkers found in the patients’ cerebrospinal fluid after treatment.

What We Don’t Know

The study’s primary result was impacted by a very large and unexpected placebo effect.
The positive results for walking were found in a subgroup analysis, which is promising but less definitive than a primary outcome.
The optimal dosing and frequency of injections for progressive MS still need to be determined.

Conclusion

This was the first randomized, placebo-controlled trial of MSC-NP therapy in progressive MS.
While it did not meet its primary goal, it provided strong evidence that the treatment is safe and offers clinically meaningful benefits for walking ability, bladder function & brain health.
The authors suggest that future studies should focus on ambulatory measures as primary goals to better capture the therapy’s potential.

Delivery Method

Each patient received six IV infusions through a standard drip, given over a period of 32 weeks.

Cell Type & Source

Autologous adipose-derived mesenchymal stem cells.
Source: The patient’s own fat tissue.
Because the cells are from the patient’s own body, there is no risk of rejection.

Cell Preparation

Patients in the trial must have previously banked their stem cells with Hope Biosciences.

Safety

The treatment was found to be safe and well-tolerated.
No deaths were reported.
The number of Serious Adverse Events was identical in both groups, with one patient in the treatment group and one patient in the placebo group experiencing one event each.

Clinical Improvements

The study successfully met its primary goal of improving quality of life.
Compared to the placebo group, patients receiving stem cells showed a statistically significant improvement in both their Physical Health and Mental Health composite scores.

Other Key Findings

• Reduced Disability: The treatment group experienced a statistically significant decrease in their disability as measured by the EDSS score, while the placebo group slightly worsened.
• Improved Mood: Patients receiving stem cells also had a statistically significant reduction in symptoms of depression as measured by the PHQ-9 questionnaire.

What We Don’t Know

The specific cell dosage and preparation details are not included.

While the results are very positive, the study was small (24 patients).
The effects of the therapy beyond one year are not yet known.

Conclusion

This successful Phase II trial shows that Hope Biosciences’ autologous adipose-derived MSC therapy is safe and effective at significantly improving quality of life, reducing disability & improving mood in patients with RRMS.
The positive and statistically significant results strongly support moving forward with larger, later-phase clinical trials to confirm these findings.

Delivery Method

Each patient received a single IV infusion of the stem cells.

Cell Type & Source

Allogeneic Placenta-Derived Mesenchymal Stem Cells (PLMSCs).
Source: The cells were derived from donated placentas after healthy births.
Placenta vs. Umbilical Cord: While both are birth tissues, the placenta is the organ that nourishes the baby in the womb. The umbilical cord is the tube that connects the baby to the placenta. They are different sources, and this study specifically used cells from the placenta itself.

Dosage

Each patient received a single dose of 3 million cells per kilogram of their body weight.

Safety

The study met its primary goal, confirming the treatment was safe.
No severe complications were reported. The only side effect was a mild, temporary headache in two of the five patients.

Clinical Improvements

• Disability (EDSS): All patients’ disability scores either improved or remained stable over the first three months.
• Cognition and Fatigue: Patients performed better on cognitive tests after the infusion and also tended to report less fatigue.
• Brain Imaging (fMRI): Brain scans showed stronger connections in areas important for memory, thinking, and spatial processing.
• Immune System: Blood tests showed positive changes, including a reduction in harmful B-cells and an increase in IL-10, a protein that helps fight inflammation.

How the Cells Worked

While not definitive, the results suggest the cells worked by providing a neuroprotective effect.
The positive changes in the blood indicate the main mechanism was likely immunomodulation, calming the overactive immune system.

What We Don’t Know

This was a very small study (5 patients) and had no placebo group, so the improvements seen could be influenced by a placebo effect.
The long-term effects of the treatment beyond six months are unknown.
The exact process for preparing the cells was not detailed.

Conclusion

This successful Phase 1 trial demonstrated that a single IV infusion of placenta-derived MSCs is safe and feasible for patients with SPMS.
The promising early results strongly support the need for larger, placebo-controlled Phase 2 trials to confirm if this therapy is truly effective.

Delivery Method

The AHSCT procedure involves using chemotherapy to wipe out the patient’s existing immune system, followed by an IV infusion of their own previously collected stem cells to rebuild a new, healthy immune system. The comparison group received one of many standard disease-modifying therapies which include injections, pills or infusions.

Cell Type & Source

Autologous Hematopoietic Stem Cells.
Source: The patient’s own blood-forming stem cells.

Cell Preparation

The process involves:

• Mobilization: Using medication to move the stem cells from the bone marrow into the bloodstream.
• Collection: Collecting the stem cells directly from the blood.

The study does not mention culturing or expanding the cells in a lab; they are collected and then re-infused.

Dosage

They don’t specify the cell dosage.

Safety

Safety is a major consideration for AHSCT. This study noted a transplant mortality rate of 1.3% in the AHSCT group, a risk that must be weighed against the potential benefits.

Primary Outcome

The study’s main goal was to compare how long it took for disability to worsen. AHSCT was clearly superior. After 5 years, 61.7% of patients who received AHSCT had not experienced any progression of their disability, compared to only 46.3% in the group treated with other standard drugs.

Other Key Findings

• Disability Trend Over Time: Over a 10-year period, the disability level of the AHSCT group remained stable, while the group on other DMTs steadily worsened.
• Disability Improvement: Patients who received AHSCT were far more likely to improve. After 3 years, 34.7% of AHSCT patients had a sustained improvement in their disability, compared to only 4.6% of patients taking other drugs.
• Relapse Rate: The rate of MS relapses was dramatically lower in the AHSCT group compared to the other DMT group.

How the Cells Worked

The researchers believe AHSCT works by using chemotherapy to eliminate the patient’s faulty immune system, followed by the stem cell infusion to “reset” it and build a new, tolerant one. They also suggest the chemotherapy drugs used can penetrate the brain and spinal cord to target the “compartmentalized inflammation” that is thought to be a key driver of disability in progressive MS.

What We Don’t Know / Limitations

This was a retrospective study, not a randomized controlled trial, so hidden biases could still be present even with the advanced statistical methods used. The control group (other DMTs) was diverse and did not include patients treated with some of the newest, most powerful MS drugs.

Conclusion

This large, real-world study provides strong evidence that AHSCT is superior to many standard MS drugs for treating active SPMS. It not only halts disability progression over the long term but also offers a significantly higher chance of sustained improvement. While the risks are serious and must be carefully considered, the findings reinforce the idea that this intensive therapy is a powerful option for people with this challenging form of MS.

Delivery Method

AHSCT is an intensive, multi-step procedure. It involves:

• A strong course of chemotherapy, known as a conditioning regimen, to wipe out the patient’s existing faulty immune system.
• An IV infusion of the patient’s own previously collected stem cells to rebuild a new, healthy immune system.

Cell Type & Source

Autologous Haematopoietic Stem Cells
Source: The patient’s own blood-forming stem cells.

Cell Preparation

• Mobilization: Doctors use medications to move the stem cells from the bone marrow into the bloodstream.
• Collection: The stem cells are then collected directly from the blood.

The study does not mention any lab culturing or expansion of the cells; they are collected and then given back to the patient.

Dosage

Patients received a minimum dose of 2 million cells per kilogram of their body weight.

Safety

• Deaths: The transplant-related mortality rate was 1.4% (5 patient deaths). The researchers stressed that all these deaths occurred in patients who already had advanced disability.
• Serious Long-Term Events: In the years after the procedure, 1.6% of patients developed a new cancer, and 7.9% developed a new autoimmune disease (most commonly thyroid-related).
• Common Complications: During the hospital stay, side effects were very common. The most frequent were high-grade fevers, significant fluid overload & viral reactivations (the Epstein-Barr virus reactivated in about 76% of monitored patients).

Clinical Improvements (Efficacy)

• The study measured Progression-Free Survival, which is the percentage of people whose disability did not get worse.
• At 2 years after transplant, 83.5% of patients had no disability progression.
• At 5 years after transplant, 62.4% of patients had no disability progression.
• The treatment was most effective for patients with RRMS.

This large, real-world study provides powerful evidence from 20 years of UK data that AHSCT is a highly effective, one-off treatment with long-lasting benefits for many patients with severe MS.

It confirms that the procedure has serious risks, which are highest in patients with advanced disability.

The authors conclude that careful patient selection is essential to properly balance the significant potential benefits against the risks.

• Delivery Method: Each patient received a single injection to transplant the stem cells directly into their spinal cord (an intraspinal injection).
• Cell Type & Source: Allogeneic Fetal Neural Stem Cells (fNSCs). Source: The cells were sourced from the brain tissue of a single, legally aborted fetus.
• Cell Preparation: The cells were isolated from the donor tissue and then cultured in the lab. They were frozen for storage at “passage 7”. Before the surgery, the cells were thawed and cultured for another 2-3 days to ensure they were healthy.
• Dosage: This was a dose-escalation study. The 12 patients were divided into four groups, receiving a single dose of 5 million, 10 million, 16 million, or 24 million cells.

• Safety: The treatment was proven to be safe. There were no deaths or serious side effects related to the stem cells. Side effects were generally mild-to-moderate and temporary, mostly related to the surgical procedure itself.
• Clinical Improvements:
  • Halted Disease Progression: Two years after the transplant, 75% of patients showed no signs of their disability getting worse.
  • Stable Motor Function: On average, patients’ walking ability and hand function did not decline over the two years.
  • Brain Lesions: In 11 of the 12 patients, the volume of MS lesions seen on MRI scans either stayed the same or decreased.
  • What Didn’t Change: The treatment did not appear to stop the overall rate of brain volume loss.
• How the Cells Worked: The transplanted cells did not turn into new nerve cells or permanently stay in the spinal cord. Instead, they had a “hit and run” effect, releasing helpful substances that created a healthier environment. Tests of the patients’ spinal fluid confirmed this, showing more molecules for nerve protection and fewer molecules that cause inflammation after the transplant.

• What We Don’t Know: This was a very small (12 patients), open-label study with no placebo group, so the positive results must be interpreted with caution. It is unknown if the benefits will last longer than two years. The best possible cell dose still needs to be determined.
• Conclusion: This Phase 1 study showed for the first time that transplanting fetal neural stem cells into the spinal cord is safe for people with advanced progressive MS. The finding that the treatment appeared to halt disease progression in most patients provides a strong reason to move forward with larger, more advanced clinical trials to prove its effectiveness.

• Delivery Method: The study tested different delivery methods and doses across three groups:
  • Group A (Combination): Received one low-dose IV infusion and one low-dose spinal injection.
  • Group B (Low Dose IV): Received two low-dose IV infusions.
  • Group C (High Dose IV): Received two high-dose IV infusions.
• Cell Type & Source: Umbilical Cord-Derived Mesenchymal Stem Cells. Source: The cells were sourced from the umbilical cords of healthy, full-term newborns.
• Cell Preparation: The umbilical cord cells were isolated and cultured. The cells were stored for use at passage 3.
• Dosage: Low dose: 0.5 million cells per kilogram of body weight. High dose: 1 million cells per kilogram of body weight.

• Safety: The treatment was proven to be safe. There were no serious adverse events reported in any of the 35 patients over the entire year. The most common side effects were mild and temporary, such as headache and fatigue.
• Clinical Improvements:
  • Disability Score (EDSS): All three groups showed a statistically significant improvement in their disability scores at both 6 and 12 months.
  • Best Results: The group that received the combination of one IV and one spinal injection had the most significant and longest-lasting improvements.
• How the Cells Worked: The stem cells worked through immunomodulation, calming and rebalancing the overactive immune system. They increased the number of “calming” immune cells (Tregs) and decreased the number of “attack” cells (Th17 cells) that drive MS inflammation.

• What We Don’t Know: The study was open-label (no placebo group), so it’s not possible to rule out a placebo effect. The number of patients in each group was small. The long-term effects of the treatment beyond one year are unknown.
• Conclusion: This successful Phase I/II study demonstrated that umbilical cord-derived MSCs are safe for patients with MS and showed strong evidence of effectiveness. It significantly improved disability and rebalanced the immune system over a one-year period. The findings suggest that a combination of IV and spinal intrathecal delivery may be the most effective approach. These positive results strongly support the need for larger, placebo-controlled trials to confirm the benefits.

• Delivery Method: The procedure involves a strong course of chemotherapy, known as a conditioning regimen, to achieve an “immunological reset” by destroying the faulty immune system.
• Cell Type & Source: Autologous Hematopoietic Stem Cells were used.
• Cell Preparation: The procedure used one of two intermediate-intensity conditioning regimens: BEAM-ATG or Cy-ATG.
• Dosage: Not explicitly mentioned in the summary text.

• Safety:
  • Adverse Events: Not the primary focus of this study, but the procedure is widely viewed as a promising alternative to traditional therapies.
  • Side Effects: Not explicitly detailed in the main findings, but the study did note that QoL scores worsened before the intervention and then improved afterward.
• Efficacy – Focus on QoL:
  • The study used the Multiple Sclerosis Impact Scale (MSIS-29), where a lower score means better QoL.
  • Physical QoL: 58% improved, while the median score decreased dramatically from 34 to 13.
  • Psychological QoL: 63% improved, while the median score decreased from 42 to 19.
  • Timing of Benefit: Improvements in both domains occurred early, within the first year following the transplant.

• This research provides clear evidence that AHSCT is associated with a clinically meaningful and long-term improvement in Quality of Life, which is something that most standard drug treatments have failed to show.
• The authors noted that this improvement starts quickly and is maintained over a median of more than five years.
• This finding supports the argument for a more widespread use of AHSCT.

The main goals of the review were to provide new insights into the MS treatment research by clearly reviewing how far along these new therapies are, how safe they are, and what problems they still face.

Key Questions:

• Is stem cell therapy a real alternative to traditional drugs? Specifically, can it successfully regrow damaged nerve tissue and fix the faulty immune response that causes MS?
• What actual results and safety issues have been seen in human trials for each different type of stem cell?
• What are the major roadblocks stopping these treatments from becoming standard care? This includes dealing with ethical concerns, preventing the body from rejecting the transplanted cells & controlling the cells to make sure they turn into the right kind of nerve tissue.

1. Effectiveness (Clinical Evidence: Does it Work?)

HSCs (Autologous Hematopoietic Stem Cell Transplantation, or aHSCT):

• Most effective therapy for people with very aggressive MS that hasn’t responded to other treatments.
• One major study reported that nearly everyone (98.8%) was still alive five years after treatment.
• Another study found that 95% of patients improved and had no further relapses or worsening.
• Shown to be better than alemtuzumab at keeping MS inactive and improving thinking/memory.

MSCs (Mesenchymal Stem Cells):

• Some small studies showed mild symptom improvement and fewer brain lesions on MRI.
• May protect nerves, suggested by lower levels of nerve-damage protein NF-L in spinal fluid.
• However, a large Phase II trial showed safety but no reduction in new MRI lesions compared to placebo.

NSCs (Neural Stem Cells):

• Early trials: 70% stronger muscles, 50% better bladder control (with MSC-derived cells).
• Two-year follow-up: 7 of 20 maintained ongoing disability improvement.
• Fetal NSC trial showed increased neurotrophic factors and anti-inflammatory proteins in spinal fluid.

2. Mechanism of Action

• Immune System Adjustment: Resets immune activity, reduces inflammation (main HSC effect).
• Differentiation: Stem cells form neurons, astrocytes, and oligodendrocytes to repair tissue.
• Nerve Support: Release neurotrophic factors to protect and sustain neural tissue.

3. Stem Cell Sources

• HSCs: Bone marrow or peripheral blood.
• MSCs: Bone marrow, adipose tissue, umbilical cord.
• NSCs: From fetal CNS tissue (too few available naturally in adults).
• iPSCs: Reprogrammed adult cells (e.g., skin or urine).

4. Dosage and Delivery

• aHSCT: Pre-transplant chemo (e.g., BEAM, cyclophosphamide, ATG).
• MSCs: Direct spinal fluid injection may be more effective than IV delivery.

5. Safety

• aHSCT: Most common short-term side effect: febrile neutropenia; no deaths in key trials. Possible long-term autoimmune risks (e.g., thyroiditis).
• MSCs: Generally safe and well-tolerated. Mild, temporary side effects (fever, headaches).
• NSCs / MSC-NPs: Safe in early trials, only mild effects reported.

6. Limitations in the Studies Reviewed

• Immune Rejection: GvHD risk in HSC transplants.
• Regulatory Challenges: Need precise control over stem cell differentiation.
• Ethical Concerns: ESCs face major ethical/religious barriers.
• Tumor Risk: iPSCs may carry genetic instability and tumor potential.

The authors state that the development of future stem cell therapies has the potential to significantly change the outlook for MS treatment.

The necessary path forward requires balanced teamwork and collaboration to take the promising results seen in lab studies and successfully turn them into safe, effective treatments for patients, ultimately offering new hope to those with MS.

The main goal was to clearly and completely study how well Mesenchymal Stem Cell therapy works and how safe it is for people with MS.

Key Questions:

• Could this stem cell treatment be a real hope for MS by being able to regrow damaged nerve tissue and fix the faulty immune response in the body?
• What actual results and safety issues have been seen in human trials specifically using MSC therapy?
• What are the main obstacles keeping this treatment from becoming a standard, approved medical care?

1. Effectiveness

• Overall Efficacy: 40.4% of MS patients improved, 32.8% remained stable, 18.1% worsened after MSC therapy.
• Cell Source Impact: Umbilical cord/placenta MSCs were more effective (56.7% improvement) vs bone marrow MSCs (38.5%).
• Follow-up Time: Improvement rates were similar whether follow-up was short (≤6 months) or long (>12 months).

2. Mechanism of Action (How the Cells Work)

Researchers didn’t specifically analyse how the cells worked across these trials.

3. Stem Cell Sources

• Bone Marrow: Most common source used.
• Umbilical Cord/Placenta: Showed greater efficacy and lower immune rejection risk.
• Adipose Tissue (Fat): Used in some trials, but less effective than umbilical cord/placenta.

4. Dosage and Delivery

• Delivery Method: IV (57.6% improvement) was superior to intrathecal (spinal) injection (32.8% improvement).
• Dosage: Varied across trials. No single optimal dose identified.

5. Safety

• Overall: Considered safe. No major complications.
• Common Side Effects: Headache (57.6%), fever (53.1%), and minor infections (urinary/respiratory).

6. Limitations in the Studies Reviewed

• Varied Results: High inconsistency makes conclusions uncertain.
• Study Quality: About half of studies only “moderate” quality.
• Publication Bias: Likely underestimates true worsening rate.

The authors state that the overall data suggests MSC therapy is an effective and safe treatment plan for patients with MS.

The necessary path forward requires:

• More research and development of new technology.
• Figuring out the best dose of MSCs.
• Running larger clinical trials to test long-term effectiveness and safety.

• The main goal was to summarize the latest evidence to get a clear picture of how well MSC therapy works for MS and how safe it is.
• How exactly do MSCs work to calm the overactive immune system in MS? Specifically, do they fix the imbalance between the “attack” cells (Th17 cells) and the “calming” cells (Tregs)?
• What changes in CSF biomarkers (proteins in the spinal fluid) can show that the treatment is protecting the nerves from damage?
• What are the real-world results and safety issues that have been seen in human trials of MSC therapy?

• Effectiveness: One large analysis reviewed by the authors showed that 40.4% of MS patients had an improvement in their disability score & another 32.8% remained stable. Another analysis found that the treatment significantly improved disability scores at the two-month mark and also reduced the total volume of brain lesions seen on MRI scans.
• Mechanism of Action: The review confirmed that MSCs seem to work primarily by calming and rebalancing the immune system (a process called immunomodulation). They help increase the body’s “calming” immune cells while reducing the “attack” cells that cause inflammation in MS.
• Stem Cell Sources: The studies used MSCs from different sources, including bone marrow and umbilical cords. The researchers noted that these differences from study to study make it hard to know if one source is better than another.
• Dosage and Delivery: The studies used different delivery methods, such as an IV or injecting them directly into the spinal fluid (intrathecal). Because of these differences, it is still not clear which method is best.
• Safety: Across all the studies they looked at, MSC therapy was found to be a safe treatment strategy. No major or life-threatening complications were identified. The most common side effects were minor and temporary, mainly headaches and fever.
• Limitations in the Studies Reviewed: The biggest problem was inconsistency — studies used different cell sources, different doses, and different delivery methods, making comparisons difficult. Many of the individual studies had a small number of patients, and most didn’t follow patients long enough to know the long-term effects of the therapy.

• The authors state that the overall evidence shows MSC therapy has significant potential as a safe and effective treatment that can help manage MS by calming the immune system and protecting the brain.
• To move forward, they say it is essential to standardize the treatment by figuring out the best cell source, dose and delivery method.
• They also stress the need for larger, high-quality clinical trials with longer follow-up times to prove the long-term benefits and safety of the therapy.

The experts endorse Autologous Haematopoietic Stem Cell Transplantation (AHSCT) for carefully selected MS patients, largely due to strong evidence that it is highly effective at stopping inflammation by “resetting” the immune system.

A. AHSCT as Escalation Therapy

Relapsing-Remitting MS (RRMS):

• AHSCT should be considered after just one powerful drug has failed.
• It’s a strong treatment. Two clinical trials showed AHSCT works better than some high-efficacy drugs like natalizumab and mitoxantrone.
• This treatment is highly successful, leading to No Evidence of Disease Activity for 70−80% of patients over the long term.

Progressive MS (Primary or Secondary):

• Not recommended for people with long-standing MS and severe disabilities.
• Should only be considered for early progressive MS if the disease is still clearly active (relapses or MRI activity).

B. Ideal Candidate Profile

• Age: Best outcomes in younger patients (<45 years).
• Disease Duration: Most effective when disease duration is short (<10 years).
• Disability Score: Recommended for patients with EDSS score <4.0.

C. Mechanism of Action

The core mechanism is “immune resetting.” AHSCT uses high-dose chemotherapy to eradicate disease-causing immune cells, followed by growth of a new, healthy immune system from transplanted stem cells, restoring immune tolerance.

Safety Data

• Risk is Lower Now: Death risk in the first 100 days has fallen to 0.3% in studies after 2005.
• Infection Risk: Highest in the first 2 years. Patients require full revaccination as they are considered “never vaccinated.”
• Secondary Autoimmunity: Risk of developing new autoimmune conditions, most often thyroiditis.
• Fertility: AHSCT can affect fertility. Patients are advised to consider egg/sperm freezing before treatment.

Limitations in the Evidence

• Weak Evidence: Much data comes from retrospective or non-randomized studies, which introduce bias.
• Follow-up: Long-term data are limited. Since AHSCT is a one-time treatment, more extended follow-up is needed to assess durability.

Ongoing Research

The optimal placement of AHSCT versus the newest drugs is still being investigated in four ongoing randomized clinical trials.