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RANDOMIZED CONTROLLED TRIAL

Allogeneic Mesenchymal Stem Cells Ameliorate Aging Frailty: A Phase II Randomized, Double-Blind, Placebo-Controlled Clinical Trial

Bryon A Tompkins, Darcy L DiFede, Aisha Khan, Ana Marie Landin, Ivonne Hernandez Schulman, Marietsy V Pujol, Alan W Heldman, Roberto Miki, Pascal J Goldschmidt-Clermont, Bradley J Goldstein, Muzammil Mushtaq, Silvina Levis-Dusseau, John J Byrnes, Maureen Lowery, Makoto Natsumeda, Cindy Delgado, Russell Saltzman, Mayra Vidro-Casiano, Moisaniel Da Fonseca, Samuel Golpanian, Courtney Premer, Audrey Medina, Krystalenia Valasaki, Victoria Florea, Erica Anderson, Jill El-Khorazaty, Adam Mendizabal, Geoff Green, Anthony A Oliva, Joshua M Hare
Journals of Gerontology. Series A, Biological Sciences and Medical Sciences 2017 October 12, 72 (11): 1513-1522
28977399

Background: Aging frailty, characterized by decreased physical and immunological functioning, is associated with stem cell depletion. Human allogeneic mesenchymal stem cells (allo-hMSCs) exert immunomodulatory effects and promote tissue repair.

Methods: This is a randomized, double-blinded, dose-finding study of intravenous allo-hMSCs (100 or 200-million [M]) vs placebo delivered to patients (n = 30, mean age 75.5 ± 7.3) with frailty. The primary endpoint was incidence of treatment-emergent serious adverse events (TE-SAEs) at 1-month postinfusion. Secondary endpoints included physical performance, patient-reported outcomes, and immune markers of frailty measured at 6 months postinfusion.

Results: No therapy-related TE-SAEs occurred at 1 month. Physical performance improved preferentially in the 100M-group; immunologic improvement occurred in both the 100M- and 200M-groups. The 6-minute walk test, short physical performance exam, and forced expiratory volume in 1 second improved in the 100M-group (p = .01), not in the 200M- or placebo groups. The female sexual quality of life questionnaire improved in the 100M-group (p = .03). Serum TNF-α levels decreased in the 100M-group (p = .03). B cell intracellular TNF-α improved in both the 100M- (p < .0001) and 200M-groups (p = .002) as well as between groups compared to placebo (p = .003 and p = .039, respectively). Early and late activated T-cells were also reduced by MSC therapy.

Conclusion: Intravenous allo-hMSCs were safe in individuals with aging frailty. Treated groups had remarkable improvements in physical performance measures and inflammatory biomarkers, both of which characterize the frailty syndrome. Given the excellent safety and efficacy profiles demonstrated in this study, larger clinical trials are warranted to establish the efficacy of hMSCs in this multisystem disorder.

Clinical Trial Registration: www.clinicaltrials.gov: CRATUS (#NCT02065245).

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