Stem Cell Transplantation for Frailty
The Journals of Gerontology, March 2017
It was reported over 50 years ago that old age is associated with depletion and loss of function of stem cells (1). Since that time, there has been extensive research confirming the deleterious effects of aging on all types of stem cells, and a growing belief that such age-related changes in stem cells further accelerate tissue and organismal aging (2–4). There are two major divisions of stem cells, embryonic stem cells and adult stem cells.
Allogeneic Mesenchymal Stem Cells Ameliorate Aging Frailty: A Phase II Randomized, Double-Blind, Placebo-Controlled Clinical Trial
The Journals of Gerontology, June 2017
There is increasing recognition of the health burden of frailty, a syndrome that increases in incidence with aging. Frailty confers an increased vulnerability to adverse health outcomes and mortality in response to stressors (1,2). Of note, the frailty syndrome is driven mostly by biological aging processes that include inflammation and stem cell dysfunction, as opposed to chronological aging (2–5). Early intervention may improve quality of life, reduce hospitalizations,
and nursing home costs (6,7). Therefore, it is increasingly important
to recognize the clinical onset of frailty, and to develop effective therapeutic strategies.
Allogeneic Human Mesenchymal Stem Cell Infusions for Aging Frailty
Journals of Gerontology, March 2017
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.
Joshua Michael Hare, M.D., F.A.C.C., F.A.H.A.
1. Golpanian S, El-Khorazaty J, Mendizabal A, DiFede DL, Suncion V, Karantalis V, Fishman JE, Ghersin E, Balkan W, Hare JM. Effect of Aging on human Mesenchymal Stem Cell Therapy in Ischemic Cardiomyopathy Patients. J Am Coll Cardiol. 2015 Jan 20;65(2):125-32. doi:10.1016/j.jacc.2014.10.040.
2. Golpanian S, DiFede DL, Pujol MV, Lowery MH, Levis-Dusseau S, Goldstein BJ, Schulman IH, Longsomboon B, Wolf A, Khan A, Heldman AW, Goldschmidt-Clermont PJ, Hare JM. Rationale and design of the allogeneiC human mesenchymal stem cells (hMSC) in patients with aging fRAilTy via intravenoUS delivery (CRATUS) study: A phase I/II, randomized, blinded and placebo controlled trial to evaluate the safety and potential efficacy of allogeneic human mesenchymal stem cell infusion in patients with aging frailty. Oncotarget. 2016 Mar 15;7(11):11899-912. doi: 10.18632/oncotarget.7727.
3. Golpanian S, DiFede DL, Khan A, Schulman IH, Landin AM, Tompkins BA, Heldman AW, Miki R, Goldstein BJ, Mushtaq M, Levis-Dusseau S, Byrnes JJ, Lowery M, Natsumeda M, Delgado C, Saltzman R, Vidro-Casiano M, Pujol MV, Da Fonseca M, Oliva AA Jr, Green G, Premer C, Medina A, Valasaki K, Florea V, Anderson E, El-Khorazaty J, Mendizabal A, Goldschmidt-Clermont PJ, Hare JM. Allogeneic Human Mesenchymal Stem Cell Infusions for Aging Frailty. J Gerontol A Biol Sci Med Sci. 2017 Apr 21. Doi: 10.1093/gerona//glx056 [Epub ahead of print]
4. Tompkins B, Difede DL, Khan A, Landin AM, Schulman I, Pujol M, Heldman A, Miki R, Goldshmidt- Clermont P, Goldstein B, Mushtaq M, Levis-Dusseau S Byrnes J, 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 A, 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. doi: 10.1093/gerona/glx137.
1. Tompkins BA, Landin AM, Florea V, Natsumeda M, Tieger AC, Balkan W, Schulman IH, Hare JM. Allogeneic Mesenchymal Stem Cells as a Treatment for Aging Frailty. Frailty and Sarcopenia.Published online 2017 Jul 17. doi:10.1093/gerona/glx137, PMCID: PMC5861900, PMID: 28977399, Inbook: Frailty and Sarcopenia – Onset, Development and Clinical Challenges.
M. PAHOR1, S.B. KRITCHEVSKY2, D.L. WATERS3, D.T. VILLAREAL4, J. MORLEY5, J.M. HARE6,
B. VELLAS7,8,9 AND THE ICFSR TASK
1. University of Florida Institute on Aging, Gainesville, FL, USA; 2. Sticht Center for Healthy Aging and Alzheimer’s Prevention. Wake Forest School of Medicine. Winston-Salem,
NC USA; 3. University of Otago, Dunedin School of Medicine, Dunedin, New Zealand; 4. Baylor College of Medicine and Michael E DeBakey VA Medical Center, Houston, TX, USA;
5. Division of Geriatrics, St. Louis, University Medical School, St. Louis, MO, USA; 6. Interdisciplinary Stem Cell Institute, University of Miami Miller School of Medicine, Miami,
FL, USA; 7. UMR1027 Inserm, F-31073, Toulouse, France; 8. University of Toulouse III, F-31073, France; 9. Gérontopôle Toulouse, Toulouse University Hospital, F-31000, Toulouse,
Corresponding author: Marco Pahor, University of Florida Institute on Aging, Gainesville, FL, USA,
Task Force members: Hidenori Arai (Obu City, Japan); Mylène Aubertin (Montréal, Canada); Jürgen Bauer (Heidelberg, Germany); Ryne Carney (Washington, USA); Brian Clark
(Athens, USA); Alfonso Cruz Jentoft (Madrid, Spain); Carla Delannoy (Vevey, Switzerland); Susanna Del Signore (Paris, France); Elsa Dent (Adelaide, Australia); Waly Dioh (Paris,
France); Roger Fielding (Boston, USA); Bertrand Fougère (St Louis, USA); Juerg Gasser (Basel, Switzerland); Geoff Green (Miami, USA); Jack Guralnik (Baltimore, USA); Hare
Joshua (Miami, USA); Aaron Hinken (King of Prussia, USA); Evgueni Ivanov (Basel, Switzerland); Naotoshi Kanemitsu (Tokyo, Japan); Kala Kaspar (Vevey, Switzerland); Tatiana
Klompenhouwer (Utrecht, The Netherlands); Stephen Kritchevsky (Winston-Salem, USA); Francesco Landi (Roma, Italy); Valérie Legrand (Nanterre, France); Yvette Luiking (Utrecht,
The Netherlands); Ram Miller (Cambridge, USA); Bradley Morgan (South San Francisco, USA); John Morley (St Louis, USA); Vikkie Mustad (Columbus, USA); David Neil (King of
Prussia, USA); Suzanne Page (Miami, USA); Marco Pahor (Gainesville, USA); Dimitris Papanicolaou (East Hanover, USA); Suzette Pereira (Columbus, USA); Claire Regard (Vevey,
Switzerland); Daniel Rooks (Cambridge, USA); Jorge Ruiz (Miami, USA); Cornel Sieber (Nürnberg, Germany); Sitra Tauscher Wisniewski (Northbrook, USA); Brooke Travnicek
(Clearwater, USA); Vellas Bruno (Toulouse, France); Dennis Villareal (Houston, USA); Debra Waters (Dunedin,New Zealand); Lixin Zhang Auberson (Basel, Switzerland)
Abstract: To reduce disability and dependence in older adults, frailty may represent an appropriate target for
intervention. While preventing frailty through lifestyle interventions may be the optimal public health approach
for many population groups, pharmacological approaches will likely be needed for individuals who meet frailty
criteria or who have comorbid conditions that contribute to and complicate the frailty syndrome, and for those
who are not compliant with lifestyle interventions. Barriers to successful development of drug treatments for
frailty include variability in how the frailty syndrome is defined, lack of agreement on the best diagnostic
tools and outcome measures, and the paucity of sensitive, reliable, and validated biomarkers. The International
Conference on Frailty and Sarcopenia Research Task Force met in Miami, Florida, on February 28, 2018, to
consider the status of treatments under development for frailty and discuss potential strategies for advancing the
field. They concluded that at the present time, there may be a more productive regulatory pathway for adjuvant
treatments or trials targeting specific functional outcomes such as gait speed. They also expressed optimism that
several studies currently underway may provide the insight needed to advance drug development for frailty.
Key words: Sarcopenia, frailty, gait speed, short physical performance battery, clinical trials.