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ABSTRACT: 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.
SUBMITTER: Golpanian S
PROVIDER: S-EPMC5861970 | biostudies-literature | 2017 Oct
REPOSITORIES: biostudies-literature
Golpanian Samuel S DiFede Darcy L DL Khan Aisha A Schulman Ivonne Hernandez IH Landin Ana Marie AM Tompkins Bryon A BA Heldman Alan W AW Miki Roberto R Goldstein Bradley J BJ Mushtaq Muzammil M Levis-Dusseau Silvina S Byrnes John J JJ Lowery Maureen M Natsumeda Makoto M Delgado Cindy C Saltzman Russell R Vidro-Casiano Mayra M Pujol Marietsy V MV Da Fonseca Moisaniel M Oliva Anthony A AA Green Geoff G Premer Courtney C Medina Audrey A Valasaki Krystalenia K Florea Victoria V Anderson Erica E El-Khorazaty Jill J Mendizabal Adam A Goldschmidt-Clermont Pascal J PJ Hare Joshua M JM
The journals of gerontology. Series A, Biological sciences and medical sciences 20171001 11
<h4>Background</h4>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.<h4>Methods</h4>In this nonrandomized, dose-escalation study, patients received a single intravenous infusion of allo-hMSCs: 20-millio ...[more]