Allogeneic Human Mesenchymal Stem Cell Infusions for Aging Frailty.
Background: Impaired endogenous stem cell repair capacity is hypothesized to be a biologic basis of frailty. Therapies that restore regenerative capacity may therefore be beneficial. This Phase 1 study evaluated the safety and potential efficacy of intravenous, allogeneic, human mesenchymal stem cell (allo-hMSC)-based therapy in patients with aging frailty. Methods: In this nonrandomized, dose-escalation study, patients received a single intravenous infusion of allo-hMSCs: 20-million (n = 5), 100-million (n = 5), or 200-million cells (n = 5). The primary endpoint was incidence of any treatment-emergent serious adverse events measured at 1 month postinfusion. The secondary endpoints were functional efficacy domains and inflammatory biomarkers, measured at 3 and 6 months, respectively. Results: There were no treatment-emergent serious adverse events at 1-month postinfusion or significant donor-specific immune reactions during the first 6 months. There was one death at 258 days postinfusion in the 200-million group. In all treatment groups, 6-minute walk distance increased at 3 months (p = .02) and 6 months (p = .001) and TNF-α levels decreased at 6 months (p < .0001). Overall, the 100-million dose showed the best improvement in all parameters, with the exception of TNF-α, which showed an improvement in both the 100- and 200-million groups (p = .0001 and p = .0001, respectively). The 100-million cell-dose group also showed significant improvements in the physical component of the SF-36 quality of life assessment at all time points relative to baseline. Conclusions: Allo-hMSCs are safe and immunologically tolerated in aging frailty patients. Improvements in functional and immunologic status suggest that ongoing clinical development of cell-based therapy is warranted for frailty.
Golpanian, S; DiFede, DL; Khan, A; Schulman, IH; Landin, AM; Tompkins, BA; Heldman, AW; Miki, R; Goldstein, BJ; Mushtaq, M; Levis-Dusseau, S; Byrnes, JJ; Lowery, M; Natsumeda, M; Delgado, C; Saltzman, R; Vidro-Casiano, M; Pujol, MV; Da Fonseca, M; Oliva, AA; Green, G; Premer, C; Medina, A; Valasaki, K; Florea, V; Anderson, E; El-Khorazaty, J; Mendizabal, A; Goldschmidt-Clermont, PJ; Hare, JM
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