Stem Cell Research For Depression in 2025

Honestly, there hasn’t been a lot of research looking at Stem Cells for Depression. Other conditions like Orthopaedic & different neurological conditions have been studied in much more detail.

But there have been a couple of new Trials launched in the past few years. We break down the current & most latest research looking at how stem cells can treat Depression.

Current Trials in 2025 looking at Stem Cell Therapy for Depression

Here is a list of current trials that are looking into Stem Cells treating Depression.

Allogeneic Bone Marrow Derived Mesenchymal Stem Cells for Bipolar Depression: Texas University, United States

You can read more about the study on their clinicaltrials.gov page.

This trial is being run by The University of Texas Health Science Center at Houston and is led by Dr. Jair Soares (MD, PhD). It is designed to find out if a single infusion of mesenchymal stem cells can help reduce depression in people with a form of bipolar disorder where standard medications haven’t worked.

Start Date and Expected Completion Date

• Start Date: April 20, 2022 (first participant enrolled)
• Expected Completion: December 1, 2026 (final data collection)
• Current Status: Recruiting participants

Participants

• Sample Size: 30 participants
  
• Age Range: 18–65 years old
  
• Condition: Diagnosed with Bipolar I or II disorder and currently in a depressive episode with a MADRS score of 25+ (indicating moderate-to-severe depression).
  
• Treatment Resistance Defined As: Not improving after 2 trials of bipolar depression medications (such as lithium, lamotrigine, quetiapine, olanzapine, lurasidone, or antidepressants).

Other criteria:

• Elevated C-reactive protein (CRP) level (>5 mg/L, a marker of inflammation).
  
• Must be able to give informed consent and remain on stable medications.
  
• Exclusions include recent MSC treatment, high suicide risk, major neurological issues, immunosuppression, or unstable serious medical conditions.

Procedure:

• Delivery Method: One IV infusion of allogeneic MSCs (from a healthy donor’s bone marrow), compared to a saline placebo.
• Timing: Single MSC infusion given within 1 week of joining the study.
• Follow-up Assessments: Participants are followed for 8 weeks, with a key additional follow-up at 26 weeks to measure longer-term effects.

Medication Rules:

• No changes to psychiatric medications during the study period.

• Anti-inflammatory drugs (like NSAIDs or steroids) are not allowed during the study.

• Cell Type Used: Allogeneic Mesenchymal Stem Cells.  Donor-derived stem cells from bone marrow, lab-prepared and purified under medical standards.

What the Study is Measuring

• Primary Outcome: Depression Severity. Change in scores on the Montgomery-Åsberg Depression Rating Scale (MADRS) (baseline, 8 weeks, 26 weeks).
• Secondary Outcome
  • Functioning: Daily functioning (FAST), overall functioning (GAF).
  • Clinical Impressions: Severity ratings for mania, depression, and overall illness (CGI-BP).
  • Cognition: Memory (California Verbal Learning Test) and problem-solving (Wisconsin Card Sorting Test).
  • Biological Markers:
    • Inflammation: The study will measure levels of inflammation in the body by testing blood markers like C-reactive protein
    • Brain-derived neurotrophic factor (BDNF): Researchers will track BDNF, a protein linked to brain health and mood regulation, to see if it changes after treatment
    • Brain activity (MRI scans): Brain scans will be used to see if there are changes in brain activity or structure after receiving the stem cell infusion.
• Safety: Suicidal ideation checks, mania risk (Young Mania Rating Scale), and adverse events.

Next Steps

• Follow-up continues until late 2026.
• Results will focus on whether MSCs reduce depression symptoms, improve daily functioning, and change biological markers of mood disorders.
• No published results yet; final analysis expected after study completion.

Alaunus Stem Cell Trial for Alcohol Use Disorder and Major Depression: United States

You can read more about this trial on their clinicaltrials.gov page.

The Alaunus trial is a research study run by the University of Texas Rio Grande Valley and led by Dr. Ihsan M. Salloum. It’s designed to test whether a single infusion of allogeneic mesenchymal stem cells can safely reduce inflammation, improve depressive symptoms and help reduce alcohol use and cravings in people living with Alcohol Use Disorder  and Major Depressive Disorder compared to a placebo.

Start Date and Expected Completion Date

• Start Date: March 18, 2018 (first participant enrolled)
• Expected Completion: July 30, 2025 (final data collection for primary outcome)
• Recruitment Status: Active, not recruiting

Procedure

• Delivery Method:
  A single peripheral intravenous (IV) infusion in a controlled medical setting.
  
• Cell Dosage:
  100 × 10⁶ (100 million) allo-hMSCs delivered in one infusion.
  
• Placebo Group:
• Participants in the control group receive a placebo infusion of 1% human albumin serum in Plasma-Lyte A.

Cell Type Used

• Allogeneic Mesenchymal Stem Cells
  These are stem cells sourced from a healthy donor and prepared under regulated medical conditions.

What the Study is Measuring

• Primary Outcome: Safety. Monitoring for serious adverse events (including suicidality or hospitalization) within one month of infusion.
• Secondary Outcomes:
  • Inflammation: hs-CRP and inflammatory biomarkers (TNF-alpha, IL-6)
  • Depression: Scores on MADRS and CGI scales
  • Alcohol Use & Cravings: Timeline Follow Back (TLFB), AUQ, and OCDS
  • Anhedonia: Snaith-Hamilton Pleasure Scale (SHAPS)
  • Cognition & Functioning: BAC-A, UPSA-B, and GAF
  • Quality of Life: Quality of Life Index (QOLI)
    

Next Steps

• Participants are followed weekly for 12 weeks, then every 3 months for 12 months.
  
• Final data analysis will evaluate safety, inflammation changes, mental health outcomes, alcohol use patterns, cognition, and daily functioning.
  
• Results are expected after study completion in mid-2025.
  
  

Reviews looking at Stem Cell Therapy for Depression

A review is a type of scientific paper where researchers summarize and analyze the results of many past studies on a topic, instead of running their own new experiment.

It’s like reading all the available evidence and then explaining what it shows overall. What’s working, what isn’t, and where the gaps are.

Unlike a clinical trial, which tests a treatment on real patients, a review pulls together findings from multiple trials to give a big-picture view.

2024 Review on Mesenchymal Stem Cell Therapy for Major Depressive Disorder: China

You can read the full review on Clausiuspress to learn more.

A team of researchers from Zhejiang University School of Medicine and The First Affiliated Hospital of Zhejiang University reviewed all available studies on using mesenchymal stem cells to treat Major Depressive Disorder. A condition projected to become the leading global cause of disease burden by 2030.

Unlike antidepressant drugs that mainly work on neurotransmitters, mesenchymal stem cells are multipotent “medicinal” cells. They can travel to damaged brain regions, release neurotrophic factors (which support and protect nerve cells), calm overactive immune responses and even help repair brain tissue.

The researchers focused on MSCs because of their two-fold potential:

1. Modulating the brain’s inflammatory and immune systems: MSCs can calm brain inflammation and regulate the immune system, both of which are closely linked to depression.
   
2. Promoting neurogenesis and neuroplasticity: MSCs help trigger neurogenesis (the growth of new nerve cells) and improve neuroplasticity (the brain’s ability to form new connections) to repair areas affected by Major Depressive Disorder (MDD).

What They Looked At

• Preclinical studies: Animal models of depression testing MSCs from bone marrow, adipose (fat), and umbilical cord.
  
• Early-phase clinical trials: Registered NIH trials and published studies involving treatment-resistant depression.

They examined both MSC transplantation and MSC-derived exosomes

What They Wanted to Find Out

• Can MSCs reduce depressive symptoms and improve cognitive function?
  
• How do MSCs work? What biological mechanisms are involved?
  
• Are MSC exosomes (cell-free therapy) effective alternatives?
  
• What is the safety profile of MSC therapy in depression?
  
• What are the optimal cell sources, dosage, and delivery routes?

What They Found

1. Effectiveness (Symptom Improvement)
   • Preclinical Studies:
     • MSCs improved depression-like behavior in animal studies by boosting hippocampal neurogenesis (the growth of new brain cells in the hippocampus) and releasing important nerve-supporting proteins like brain-derived neurotrophic factor (BDNF), nerve growth factor (NGF) and insulin-like growth factor-1 (IGF-1).
       
     • In Flinders Sensitive Line (FSL) rats (a common model for depression) MSC transplantation reduced depressive behaviors and increased neural stem cell activity in the hippocampus.
   • Human Trials (Published):
     • Cord Blood Cell Infusion Study (13 women): Receiving 4 weekly infusions lowered Beck Depression Inventory (BDI) scores from 28.66 to 14.71. Also improved mood and boosted cognitive function, including memory, processing speed, and learning.
       
     • MSC + Standard Therapy Study (60 patients): Adding human umbilical cord MSCs to regular depression treatment significantly reduced Hamilton Depression Scale scores, lowered inflammation markers (IL-1β, IL-6, TNF-α). Increased 5-HT (serotonin), NE (norepinephrine) and BDNF (a nerve-supporting protein).
2. Mechanism of Action
   • Neuroprotection: MSCs secrete factors like BDNF and NGF, which repair damaged neurons and strengthen synaptic connections.
     
   • Neurogenesis: MSCs stimulate the hippocampus (critical for mood regulation) to generate new neurons.
     
   • Immune Regulation: MSCs reduce excessive pro-inflammatory cytokines linked to depression and calm overactive immune pathways such as the NLRP3 inflammasome.
     
   • Exosome Effects: MSC-derived exosomes cross the blood-brain barrier, delivering growth factors and microRNAs to damaged brain tissue without requiring live cell transplantation.
3. Stem Cell Sources
   • MSCs were sourced from:
     • Bone marrow (BM-MSCs)
       
     • Adipose tissue (ADSCs)
       
     • Umbilical cord (hUC-MSCs)
   • Umbilical cord MSCs and their exosomes are favored due to easy collection, low immune risk, and strong neuroprotective effects.
4. Dosage and Delivery
   • Human Trials: Used IV infusions of 100 Million Stem Cells per dose (single or multiple infusions).
     
   • Preclinical Studies: MSCs were often injected directly into brain regions or ventricles in animal models to assess localized effects.
     
   • Exosome Therapy: Seen as a future alternative due to fewer risks and ability to cross the blood-brain barrier.
5. Safety
   • Low Risk Profile:
     • No increase in serious adverse events in Phase I/II trials.
       
     • Mild transient effects (e.g., hot flushes) resolved quickly.
   • Tumor Risk: No evidence in trials, but long-term monitoring is needed, as in vitro MSC culture has raised theoretical concerns.
6. Limitations in the Studies Reviewed
   • Only two published human clinical trials; most evidence is still preclinical or early-phase.
     
   • Variation in cell sources, dosages, and protocols limits comparability across studies.
     
   • Larger, standardized Phase III trials are needed to confirm optimal protocols.

What They Concluded

• MSCs and MSC-derived exosomes represent a novel, multipronged therapy for depression that:
  • Repairs brain tissue and synapses: MSCs help fix damaged brain tissue and strengthen synapses (the connections between nerve cells).
    
  • Promotes neurogenesis: The process of creating new nerve cells in the brain.
    
  • Reduces immune-driven inflammation: MSCs calm inflammation caused by the immune system, which is strongly linked to depression.
• Best Use Cases: Treatment-resistant depression and patients with incomplete remission from standard drugs.
• Next Steps:
  • Conduct large-scale clinical trials with standardized MSC sources and dosing.
    
  • Explore cell-free exosome therapy for improved safety and scalability.
    
  • Investigate long-term safety and durability of benefits.

Bottom Line: MSC therapy offers hope for depression patients who don’t respond to conventional treatments by targeting both the brain’s biology and immune system dysfunction. While promising, it is still early-stage and needs rigorous testing before routine use.

2024 Review on Stem Cell Therapy for Psychiatric Disorders: Spain

You can read the full review on Pubmed to learn more.

An international team of researchers, led by Rosa Villanueva, reviewed available studies on using stem cell therapy to treat major psychiatric conditions, including bipolar disorder, major depression, schizophrenia and autism spectrum disorder.

What They Looked At

The review evaluated numerous preclinical animal studies and human clinical trials involving patients with bipolar disorder, major depression, schizophrenia and autism spectrum disorder.

The exact total number of studies and patients was not aggregated, but the review highlighted various study designs.

These included:

• Randomized controlled trials (studies where patients are randomly assigned to different treatment groups)
• Pilot studies (small-scale studies to test feasibility and initial safety)
• Case reports (detailed reports of individual patients)

Many patients in these studies had conditions that didn’t respond well to standard drug therapies.

What They Wanted to Find Out

• What is the current status of stem cell therapy for these psychiatric disorders?
• How is stem cell technology helping us better understand the biology and causes of these disorders?
• What are the safety profiles and potential effectiveness of stem cell applications in human patients?
• What are the primary mechanisms by which stem cells exert their therapeutic effects in the brain?

What They Found

1. Effectiveness
   • Bipolar Disorder: While in vitro studies using stem cells are greatly advancing the understanding how Bipolar Disorder develops and how mood stabilizers work, human clinical trials for stem cell therapy in BD are still in very early stages, with no published results yet.
   • Major Depressive Disorder: Preclinical animal studies show promising results. A small human pilot study involving 16 female patients with treatment-resistant depression showed improvements in cognitive impairment (problems with thinking, memory, and concentration) and helped overcome their resistance to conventional treatment.
   • Schizophrenia: Preclinical studies are encouraging. One human pilot study with 15 patients found increased cerebral cortical activity (activity in the outer layer of the brain) after stem cell treatment, suggesting improved neuronal plasticity.
   • Autism Spectrum Disorder: Many preclinical and human trials have been conducted. Most reported improvements in autism symptoms without major adverse events.
     
     Some studies showed positive changes in electroencephalogram (a test that measures brain electrical activity) and brain connectivity (how different brain regions communicate). However, one RCT reported no therapeutic efficacy, which the review suggests might be due to the specific treatment protocol used.
2. Mechanism of Action
   •  Immune Regulation: Stem cells appear to regulate the immune system, reducing inflammation in the brain and protecting vital brain support cells like astroglia and microglia from damage.
   • Trophic Effects: They release beneficial factors that promote neuronal plasticity and potentially stimulate endogenous neurogenesis (the natural process of creating new brain cells).
   • Cell Replacement: While theoretically possible, direct replacement of damaged neural tissue by grafting (transplanting cells directly into tissue) is still at an early preclinical stage for psychiatric disorders.
   • Exosomes:There’s a growing idea that the beneficial effects of stem cells might even be achieved by using only the exosomes, potentially offering a cell-free therapeutic approach.
3. Safety
   • Overall, the reviewed human pilot studies found stem cell therapy to be safe and free of serious adverse events.
4. Limitations in the Studies Reviewed
   • Many human studies are small pilot studies, often lacking control groups
   • There is a significant reliance on preclinical animal studies for conditions like major depressive disorder, meaning more human data is needed.
   • A key challenge is the difficulty of stem cells overcoming the blood-brain barrier (a protective filter that prevents substances in the blood from entering the brain) through non-invasive methods

What They Concluded

Stem cell technology is in early stages for human clinical applications. It’s showing encouraging, safe results in pilot studies for psychiatric conditions.

The main ways stem cells work seem to involve controlling the immune system, protecting the brain from inflammation, and helping the brain form new connections and adapt.

2021 Review on Mesenchymal Stem Cell Therapy for Depression: Brazil

You can read the full reviewon Pubmed to learn more.

A team of researchers in Brazil from institutions including the Brain Institute of Rio Grande do Sul and the Federal University of Santa Maria conducted a narrative review on the potential use of mesenchymal stem cells and related cell-based products to treat depression, especially treatment-resistant cases.

Depression is one of the leading causes of disability worldwide, and about one-third of patients fail to respond to standard antidepressants. The researchers focused on MSCs due to their dual action of reducing brain inflammation and promoting neuroregeneration, mechanisms not targeted by current medications.

What They Looked At

The review analyzed:

• Preclinical studies in animal models of depression using MSCs, bone marrow mononuclear cells (BMMCs) and stem cell-derived exosomes.
  
• Registered clinical trials investigating MSCs or exosomes in patients with major depressive disorder, bipolar depression, or refractory depression.
  

What They Wanted to Find Out

• Can stem cells reduce depressive symptoms and improve neurobiology linked to depression?
  
• How do stem cells reduce brain inflammation and help the brain work better?
  
• Are these therapies safe and feasible for psychiatric use?
  
• What is the current progress in translating animal findings into human clinical trials?

What They Found

1. Effectiveness (Preclinical, don’t take too much stock in this)
   • BMMCs in Rats: Helped depressed rats act normally again (measured by sucrose preference), lowered harmful inflammation signals like IL-1β, IL-6, and TNF-α and boosted helpful ones like IL-10 and BDNF, which supports brain health.
     
   • Adipose-Derived MSCs (ADSCs): Helped reduce depression-like behavior in animals by balancing inflammation signals, boosting brain repair proteins like BDNF, and calming overactive immune cells in the brain called microglia.
     
   • Encapsulated MSCs (Kyoto rats): In rats bred to resist normal depression treatments, stem cells improved mood-like behavior within two weeks and helped grow new brain cells in an area linked to memory and emotions (the hippocampus).
     
   • Exosome Therapy: Exosomes, carrying molecules (miR-26a and miR-207), helped lower brain inflammation, reduce cell damage and ease depression-like behavior in animals.
2. Mechanism of Action
   • Immunomodulation: Stem cells calm the immune system by turning down harmful inflammation signals (like IL-1β, IL-6, TNF-α) and boosting protective ones like IL-10, helping brain immune cells (microglia) shift into a healing, anti-inflammatory state.
     
   • Neurotrophic Support: Stem cells boost key brain growth proteins (BDNF, VEGF, FGF2, CNTF) that help create new brain cells and repair connections between them.
     
   • Exosome Effects: Exosomes carry molecules (miRNAs) that turn off harmful inflammation signals (NF-κB), lower cell damage from stress and help repair brain cells.
     
   • Oxidative Stress Reduction: Stem cells increase antioxidants (like SOD) that protect the brain and lower signs of cell damage, such as DNA harm markers like 8′2-deoxyguanosine.
3. Human Clinical Trials
   • Four early-stage clinical trials are investigating MSCs or exosomes in depression:
   • No published success rates in humans yet; all studies are focused on safety, tolerability, and preliminary efficacy.
4. Safety
   • Animal studies show no tumorigenic or severe adverse effects.
     
   • MSCs are considered low-immunogenic, making allogeneic use feasible.
     
   • Human trial safety data are still pending.
5. Limitations
   • No published clinical results yet.
     
   • Translating results from controlled animal models to complex human depression cases (often polypharmacy and comorbid) is challenging.

What They Concluded

MSC therapy could become a novel, biologically targeted treatment for depression, especially for treatment-resistant cases.

• It targets core inflammatory and neurodegenerative processes linked to depression.
  
• Preclinical evidence is strong, but human studies are needed to establish true success rates, safety, and standardized protocols.
  
• The authors emphasize more Phase II/III trials and a focus on exosome-based approaches as a promising, cell-free alternative
  

Conclusion

As mentioned at the start of this article, this is a really early stage part of Stem Cell Research. A lot of the current data is coming from pre-clinical, animal studies which don’t always have the same results for humans. That being said, we’ve summarized some of the key findings from the latest data in 2025:

Effectiveness shows early promise:

• Preclinical studies consistently demonstrate reduced depressive behaviors, brain repair and improved neuroplasticity.
  
• Small human trials report mood improvements, better cognitive function, and decreased inflammation, especially in treatment-resistant depression.
  
• Exosome-based (cell-free) therapies are emerging as a potential future alternative.
  

How it works:
 In all studies, MSCs help by calming brain inflammation, repairing neural pathways and boosting brain growth factors (like BDNF). They act through immune regulation and neuroprotection, not by replacing brain tissue.

Safety is encouraging:
 Early human trials report mild, temporary effects and no serious adverse events. However, most evidence is still preclinical, with only a few small human studies.

If you’re considering stem cell therapy for depression, keep in mind: real-world clinics may not follow the rigorous safety and dosing protocols used in trials. While early results are hopeful, this is still experimental, and large-scale studies are needed to confirm benefits and long-term safety.