Allogeneic Human Mesenchymal Stem Cell Infusions for Aging Frailty

Samuel Golpanian, Darcy L. DiFede, Aisha Khan, Ivonne H Schulman, Ana Marie Landin, Bryon A. Tompkins, Alan W. Heldman, Roberto Miki, Bradley J Goldstein, Muzammil Mushtaq, Silvina Levis, John Byrnes, Maureen Lowery, Makoto Natsumeda, Cindy Delgado, Russell Saltzman, Mayra Vidro-Casiano, Marietsy V. Pujol, Moisaniel Da Fonseca, Anthony A. OlivaGeoff Green, Courtney Premer, Audrey Medina, Krystalenia Valasaki, Victoria Florea, Erica Anderson, Jill El-Khorazaty, Adam Mendizabal, Pascal Goldschmidt-Clermont, Joshua Hare

Research output: Contribution to journalArticle

19 Citations (Scopus)

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.

Original languageEnglish (US)
Pages (from-to)1505-1512
Number of pages8
JournalThe journals of gerontology. Series A, Biological sciences and medical sciences
Volume72
Issue number11
DOIs
StatePublished - Oct 12 2017

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Cell Aging
Mesenchymal Stromal Cells
Cell- and Tissue-Based Therapy
Therapeutics
Intravenous Infusions
Stem Cells
Biomarkers
Quality of Life
Tissue Donors
Safety
Incidence

Keywords

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

ASJC Scopus subject areas

  • Aging
  • Geriatrics and Gerontology

Cite this

Allogeneic Human Mesenchymal Stem Cell Infusions for Aging Frailty. / Golpanian, Samuel; DiFede, Darcy L.; Khan, Aisha; Schulman, Ivonne H; Landin, Ana Marie; Tompkins, Bryon A.; Heldman, Alan W.; Miki, Roberto; Goldstein, Bradley J; Mushtaq, Muzammil; Levis, Silvina; Byrnes, John; Lowery, Maureen; Natsumeda, Makoto; Delgado, Cindy; Saltzman, Russell; Vidro-Casiano, Mayra; Pujol, Marietsy V.; Da Fonseca, Moisaniel; Oliva, Anthony A.; Green, Geoff; Premer, Courtney; Medina, Audrey; Valasaki, Krystalenia; Florea, Victoria; Anderson, Erica; El-Khorazaty, Jill; Mendizabal, Adam; Goldschmidt-Clermont, Pascal; Hare, Joshua.

In: The journals of gerontology. Series A, Biological sciences and medical sciences, Vol. 72, No. 11, 12.10.2017, p. 1505-1512.

Research output: Contribution to journalArticle

Golpanian, S, DiFede, DL, Khan, A, Schulman, IH, Landin, AM, Tompkins, BA, Heldman, AW, Miki, R, Goldstein, BJ, Mushtaq, M, Levis, S, Byrnes, J, 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, P & Hare, J 2017, 'Allogeneic Human Mesenchymal Stem Cell Infusions for Aging Frailty', The journals of gerontology. Series A, Biological sciences and medical sciences, vol. 72, no. 11, pp. 1505-1512. https://doi.org/10.1093/gerona/glx056
Golpanian, Samuel ; DiFede, Darcy L. ; Khan, Aisha ; Schulman, Ivonne H ; Landin, Ana Marie ; Tompkins, Bryon A. ; Heldman, Alan W. ; Miki, Roberto ; Goldstein, Bradley J ; Mushtaq, Muzammil ; Levis, Silvina ; Byrnes, John ; Lowery, Maureen ; Natsumeda, Makoto ; Delgado, Cindy ; Saltzman, Russell ; Vidro-Casiano, Mayra ; Pujol, Marietsy V. ; Da Fonseca, Moisaniel ; Oliva, Anthony A. ; Green, Geoff ; Premer, Courtney ; Medina, Audrey ; Valasaki, Krystalenia ; Florea, Victoria ; Anderson, Erica ; El-Khorazaty, Jill ; Mendizabal, Adam ; Goldschmidt-Clermont, Pascal ; Hare, Joshua. / Allogeneic Human Mesenchymal Stem Cell Infusions for Aging Frailty. In: The journals of gerontology. Series A, Biological sciences and medical sciences. 2017 ; Vol. 72, No. 11. pp. 1505-1512.
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T1 - Allogeneic Human Mesenchymal Stem Cell Infusions for Aging Frailty

AU - Golpanian, Samuel

AU - DiFede, Darcy L.

AU - Khan, Aisha

AU - Schulman, Ivonne H

AU - Landin, Ana Marie

AU - Tompkins, Bryon A.

AU - Heldman, Alan W.

AU - Miki, Roberto

AU - Goldstein, Bradley J

AU - Mushtaq, Muzammil

AU - Levis, Silvina

AU - Byrnes, John

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

AU - Hare, Joshua

PY - 2017/10/12

Y1 - 2017/10/12

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.

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KW - Inflammation

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