Abstract
BACKGROUND: Alzheimer's disease (AD) presents significant unmet medical needs with no effective therapeutic options. Current pharmacological treatments provide only symptomatic relief and do not prevent the ongoing neurodegeneration. Cell therapies using mesenchymal stem cells (MSCs) are being widely investigated for its potential in treating AD but remain unverified. This review aimed to evaluate therapeutic effects of MSCs on AD patients through a review of clinical trial literatures. METHODS: Publications and registered clinical trials from January 2011 to June 2025 were collected from the international databases (ClinicalTrials.gov, PubMed, Web of Science, SCOPUS) using the keywords of "Alzheimer's disease", "mesenchymal stem cells", and "clinical trials". After initial screening and sorting, 17 clinical trials and 4 related papers were finally selected for in-depth analysis. RESULTS: The 17 clinical trials were mostly early stages with 4 phase 1 (23.5%), 9 phases 1/2 (52.9%), 3 phase 2 (17.7%), and 1 pilot phase (5.9%). The source of MSCs included allogeneic umbilical cord blood (UCB) in 5 trials (29.4%), autologous adipose tissue in 4 (23.5%), allogeneic umbilical cord (UC) in 3 (17.6%), allogeneic bone marrow (BM) in 3 (17.6%), allogeneic placenta in 1 (5.9%) and 1 unknown (5.9%). Administration routes were primarily intravenous (IV) infusion in 12 trials (70.6%), intracerebroventricular (ICV) infusion via Ommaya reservoir in 3 (17.6%), and stereotactic brain injection (SBI) in 2 (11.8%). Among the 17 clinical trials, outcome data of 7 trials have been reported in 4 clinical papers and 1 clinical results posted in ClincalTrials.gov: 4 trials using UCB MSCs (NEUROSTEM-AD) in 2 papers, 2 trials using BM MSCs (Lomecel-B) in 2 papers and 1 trial using adipose MSCs (AstroStem) in ClinicalTrials.gov. All 5 reports using different cell types, administration routes or dosages claimed the safety of MSCs administration. As for the therapeutic efficacy, 2 reports using Lomecel-B reported meaningful improvement in AD pathophysiology or cognitive functions, while the other 3 reports using NEUROSTEM-AD or AstroStem failed to show statistically significant efficacy. CONCLUSION: The analysis of 17 clinical trials and 5 relevant clinical outcomes showed that MSCs therapy if feasible and generally safe in AD patients. There are indications of potential therapeutic benefits such as improved cognitive function or quality of life measures in some AD patients. However, its therapeutic efficacy has not been proven definitely due to small size of subjects, variations in dosage, MSCs source, and administration scheme (route, timing, and frequency). Larger subject sizes and well-controlled trials are needed to provide more conclusive evidence.