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// Samuel Golpanian 1,2 , Darcy L. DiFede 1 , Marietsy V. Pujol 1 , Maureen H. Lowery 3 , Silvina Levis-Dusseau 3,5 , Bradley J. Goldstein 1,7 , Ivonne H. Schulman 1,3,6 , Bangon Longsomboon 1 , Ariel Wolf 1 , Aisha Khan 1 , Alan W. Heldman 1,3,4 , Pascal J. Goldschmidt-Clermont 3,4 and Joshua M. Hare 1,3,4 1 Interdisciplinary Stem Cell Institute, University of Miami Miller School of Medicine, Miami, FL, USA 2 Department of Surgery, University of Miami Miller School of Medicine, Miami, FL, USA 3 Department of Medicine, University of Miami Miller School of Medicine, Miami, FL, USA 4 Division of Cardiology, University of Miami Miller School of Medicine, Miami, FL, USA 5 Division of Endocrinology, University of Miami Miller School of Medicine, Miami, FL, USA 6 Division of Nephrology, University of Miami Miller School of Medicine, Miami, FL, USA 7 Department of Otolaringology, University of Miami Miller School of Medicine, Miami, FL, USA Correspondence to: Joshua M. Hare, email: // Keywords : aging, frailty, mesenchymal stem cells, allogeneic, Gerotarget Received : December 20, 2015 Accepted : January 30, 2016 Published : February 25, 2016 Abstract Frailty is a syndrome associated with reduced physiological reserves that increases an individual’s vulnerability for developing increased morbidity and/or mortality. While most clinical trials have focused on exercise, nutrition, pharmacologic agents, or a multifactorial approach for the prevention and attenuation of frailty, none have studied the use of cell-based therapies. We hypothesize that the application of allogeneic human mesenchymal stem cells (allo-hMSCs) as a therapeutic agent for individuals with frailty is safe and efficacious. The CRATUS trial comprises an initial non-blinded phase I study, followed by a blinded, randomized phase I/II study (with an optional follow-up phase) that will address the safety and pre-specified beneficial effects in patients with the aging frailty syndrome. In the initial phase I protocol, allo-hMSCs will be administered in escalating doses via peripheral intravenous infusion (n=15) to patients allocated to three treatment groups: Group 1 (n=5, 20 million allo-hMSCs), Group 2 (n=5, 100 million allo-hMSCs), and Group 3 (n=5, 200 million allo-hMSCs). Subsequently, in the randomized phase, allo-hMSCs or matched placebo will be administered to patients (n=30) randomly allocated in a 1:1:1 ratio to one of two doses of MSCs versus placebo: Group A (n=10, 100 million allo-hMSCs), Group B (n=10, 200 million allo-hMSCs), and Group C (n=10, placebo). Primary and secondary objectives are, respectively, to demonstrate the safety and efficacy of allo-hMSCs administered in frail older individuals. This study will determine the safety of intravenous infusion of stem cells and compare phenotypic outcomes in patients with aging frailty.