TY - JOUR
T1 - Allogeneic Human Mesenchymal Stem Cell Infusions for Aging Frailty
AU - Golpanian, Samuel
AU - Difede, Darcy L.
AU - Khan, Aisha
AU - Schulman, Ivonne Hernandez
AU - Landin, Ana Marie
AU - Tompkins, Bryon A.
AU - Heldman, Alan W.
AU - Miki, Roberto
AU - Goldstein, Bradley J.
AU - Mushtaq, Muzammil
AU - Levis-Dusseau, Silvina
AU - Byrnes, John J.
AU - Lowery, Maureen
AU - Natsumeda, Makoto
AU - Delgado, Cindy
AU - Saltzman, Russell
AU - Vidro-Casiano, Mayra
AU - Pujol, Marietsy V.
AU - Da Fonseca, Moisaniel
AU - Oliva, Anthony A.
AU - Green, Geoff
AU - Premer, Courtney
AU - Medina, Audrey
AU - Valasaki, Krystalenia
AU - Florea, Victoria
AU - Anderson, Erica
AU - El-Khorazaty, Jill
AU - Mendizabal, Adam
AU - Goldschmidt-Clermont, Pascal J.
AU - Hare, Joshua M.
N1 - Publisher Copyright:
© The Author 2017. Published by Oxford University Press on behalf of The Gerontological Society of America.
PY - 2017/11/1
Y1 - 2017/11/1
N2 - 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.
AB - 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.
KW - Cell-based therapy
KW - Inflammation
KW - Physical function
KW - Regenerative medicine
UR - http://www.scopus.com/inward/record.url?scp=85027447228&partnerID=8YFLogxK
U2 - 10.1093/gerona/glx056
DO - 10.1093/gerona/glx056
M3 - Article
C2 - 28444181
AN - SCOPUS:85027447228
SN - 1079-5006
VL - 72
SP - 1505
EP - 1512
JO - Journals of Gerontology - Series A Biological Sciences and Medical Sciences
JF - Journals of Gerontology - Series A Biological Sciences and Medical Sciences
IS - 11
ER -