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J Gerontol A Biol Sci Med Sci. 2017 Oct 12;72(11):1505-1512. doi: 10.1093/gerona/glx056.

Allogeneic Human Mesenchymal Stem Cell Infusions for Aging Frailty.

Author information

1
The Interdisciplinary Stem Cell Institute.
2
Department of Surgery, University of Miami Miller School of Medicine, Florida.
3
Longeveron LLC, Miami, Florida.
4
Department of Medicine, University of Miami Miller School of Medicine, Florida.
5
The Emmes Corporation, Rockville, Maryland.

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.

KEYWORDS:

Cell-based therapy; Inflammation; Physical function; Regenerative medicine

PMID:
28444181
PMCID:
PMC5861970
DOI:
10.1093/gerona/glx056
[Indexed for MEDLINE]
Free PMC Article

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