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Allogeneic Mesenchymal Stem Cells Ameliorate Aging Frailty: A Phase II Randomized, Double-Blind, Placebo-Controlled Clinical Trial.

Publication ,  Journal Article
Tompkins, BA; DiFede, DL; Khan, A; Landin, AM; Schulman, IH; Pujol, MV; Heldman, AW; Miki, R; Goldschmidt-Clermont, PJ; Goldstein, BJ; Green, G ...
Published in: J Gerontol A Biol Sci Med Sci
October 12, 2017

BACKGROUND: Aging frailty, characterized by decreased physical and immunological functioning, is associated with stem cell depletion. Human allogeneic mesenchymal stem cells (allo-hMSCs) exert immunomodulatory effects and promote tissue repair. METHODS: This is a randomized, double-blinded, dose-finding study of intravenous allo-hMSCs (100 or 200-million [M]) vs placebo delivered to patients (n = 30, mean age 75.5 ± 7.3) with frailty. The primary endpoint was incidence of treatment-emergent serious adverse events (TE-SAEs) at 1-month postinfusion. Secondary endpoints included physical performance, patient-reported outcomes, and immune markers of frailty measured at 6 months postinfusion. RESULTS: No therapy-related TE-SAEs occurred at 1 month. Physical performance improved preferentially in the 100M-group; immunologic improvement occurred in both the 100M- and 200M-groups. The 6-minute walk test, short physical performance exam, and forced expiratory volume in 1 second improved in the 100M-group (p = .01), not in the 200M- or placebo groups. The female sexual quality of life questionnaire improved in the 100M-group (p = .03). Serum TNF-α levels decreased in the 100M-group (p = .03). B cell intracellular TNF-α improved in both the 100M- (p < .0001) and 200M-groups (p = .002) as well as between groups compared to placebo (p = .003 and p = .039, respectively). Early and late activated T-cells were also reduced by MSC therapy. CONCLUSION: Intravenous allo-hMSCs were safe in individuals with aging frailty. Treated groups had remarkable improvements in physical performance measures and inflammatory biomarkers, both of which characterize the frailty syndrome. Given the excellent safety and efficacy profiles demonstrated in this study, larger clinical trials are warranted to establish the efficacy of hMSCs in this multisystem disorder. CLINICAL TRIAL REGISTRATION: www.clinicaltrials.gov: CRATUS (#NCT02065245).

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Published In

J Gerontol A Biol Sci Med Sci

DOI

EISSN

1758-535X

Publication Date

October 12, 2017

Volume

72

Issue

11

Start / End Page

1513 / 1522

Location

United States

Related Subject Headings

  • Treatment Outcome
  • Transplantation, Homologous
  • Regenerative Medicine
  • Middle Aged
  • Mesenchymal Stem Cell Transplantation
  • Male
  • Infusions, Intravenous
  • Immunity, Innate
  • Humans
  • Gerontology
 

Citation

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Tompkins, B. A., DiFede, D. L., Khan, A., Landin, A. M., Schulman, I. H., Pujol, M. V., … Hare, J. M. (2017). Allogeneic Mesenchymal Stem Cells Ameliorate Aging Frailty: A Phase II Randomized, Double-Blind, Placebo-Controlled Clinical Trial. J Gerontol A Biol Sci Med Sci, 72(11), 1513–1522. https://doi.org/10.1093/gerona/glx137
Tompkins, Bryon A., Darcy L. DiFede, Aisha Khan, Ana Marie Landin, Ivonne Hernandez Schulman, Marietsy V. Pujol, Alan W. Heldman, et al. “Allogeneic Mesenchymal Stem Cells Ameliorate Aging Frailty: A Phase II Randomized, Double-Blind, Placebo-Controlled Clinical Trial.J Gerontol A Biol Sci Med Sci 72, no. 11 (October 12, 2017): 1513–22. https://doi.org/10.1093/gerona/glx137.
Tompkins BA, DiFede DL, Khan A, Landin AM, Schulman IH, Pujol MV, et al. Allogeneic Mesenchymal Stem Cells Ameliorate Aging Frailty: A Phase II Randomized, Double-Blind, Placebo-Controlled Clinical Trial. J Gerontol A Biol Sci Med Sci. 2017 Oct 12;72(11):1513–22.
Tompkins, Bryon A., et al. “Allogeneic Mesenchymal Stem Cells Ameliorate Aging Frailty: A Phase II Randomized, Double-Blind, Placebo-Controlled Clinical Trial.J Gerontol A Biol Sci Med Sci, vol. 72, no. 11, Oct. 2017, pp. 1513–22. Pubmed, doi:10.1093/gerona/glx137.
Tompkins BA, DiFede DL, Khan A, Landin AM, Schulman IH, Pujol MV, Heldman AW, Miki R, Goldschmidt-Clermont PJ, Goldstein BJ, Mushtaq M, Levis-Dusseau S, Byrnes JJ, Lowery M, Natsumeda M, Delgado C, Saltzman R, Vidro-Casiano M, Da Fonseca M, Golpanian S, Premer C, Medina A, Valasaki K, Florea V, Anderson E, El-Khorazaty J, Mendizabal A, Green G, Oliva AA, Hare JM. Allogeneic Mesenchymal Stem Cells Ameliorate Aging Frailty: A Phase II Randomized, Double-Blind, Placebo-Controlled Clinical Trial. J Gerontol A Biol Sci Med Sci. 2017 Oct 12;72(11):1513–1522.
Journal cover image

Published In

J Gerontol A Biol Sci Med Sci

DOI

EISSN

1758-535X

Publication Date

October 12, 2017

Volume

72

Issue

11

Start / End Page

1513 / 1522

Location

United States

Related Subject Headings

  • Treatment Outcome
  • Transplantation, Homologous
  • Regenerative Medicine
  • Middle Aged
  • Mesenchymal Stem Cell Transplantation
  • Male
  • Infusions, Intravenous
  • Immunity, Innate
  • Humans
  • Gerontology