Mesenchymal Stem-cell Therapy in Mild-to-moderate Alzheimer’s Disease: Safety, Cognitive Efficacy, and Biomarker Signals from Controlled Human Trials
Aditi Narsinghpura1, Salma Younas2, Abhigna Mallepally3, Sankranthi Sarath Chandra4, Aditya Jain5, Sweta Sahu6
1Kasturba medical college, Mangalore, Manipal University, 2University of the Punjab, 3Gandhi Hospital, Hyderabad, 4Kurnool Medical College, 5Shyam Shah Medical College, Rewa, 6JJM Medical College
Objective:
To evaluate the safety, cognitive efficacy, and biomarker effects of mesenchymal stem-cell (MSC) therapy in adults with mild-to-moderate Alzheimer’s disease by synthesizing evidence from randomized and controlled human trials, providing an updated appraisal of therapeutic potential and guiding design priorities for future biomarker-driven phase II/III studies.
Background:
Mesenchymal stem cell (MSC) therapy is an emerging disease-modifying strategy for Alzheimer’s disease (AD). We synthesized controlled and randomized human trials to appraise safety, cognitive efficacy, and biomarker effects in adults with mild-to-moderate AD.
Design/Methods:
We integrated two independent evidence pulls (ClinicalTrials.gov–based and Elicit/OpenAlex–based). Eligible studies were randomized controlled trials (RCTs) or controlled clinical trials (CCTs) of MSCs (any source/route) in adults with mild-to-moderate AD that reported safety, cognition, or biomarkers. Data elements covered trial design, population, MSC product/source/route, follow-up, adverse events (AEs), cognitive outcomes (ADAS-Cog, MMSE), and biomarkers (neuroimaging, CSF/blood).
Results:
Eight phase I–IIa controlled trials evaluated umbilical-cord, bone-marrow, or adipose-derived MSCs delivered intravenously, intraventricularly, or intracerebrally, with follow-up of 12 weeks–12 months. Safety was primary in most. One double-blind RCT reported more AEs with MSCs (6/11 vs 3/10), including three serious events but no treatment-related deaths. Other studies (Lomecel-B/LMSCs) found MSCs safe without dose-limiting toxicity. Cognitive results were mixed: low-dose Lomecel-B improved MMSE by 2.69 points (P = 0.018) with QoL gains; laromestrocel showed a nonsignificant change (0.38; 95% CI −0.06 to 0.82) and MMSE–hippocampal correlation (r = 0.41). Biomarker data were incomplete but suggested slowed brain/hippocampal atrophy (~48–62%) and transient vascular-inflammatory effects; amyloid/tau findings were inconsistent.
Conclusions:
MSC therapy for mild-to-moderate AD shows an overall acceptable short-term safety profile, with one study noting higher AEs in MSC recipients. Cognitive outcomes were heterogeneous with isolated short-term gains, and imaging/biomarker signals suggest slower atrophy and vascular modulation. Evidence remains limited; larger, biomarker-driven phase II/III RCTs are needed to confirm efficacy.
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