Frailty and Rejuvenation with Stem Cells: Therapeutic Opportunities and Clinical Challenges

Frailty, one appealing target for improving successful aging of the elderly population, is a common clinical syndrome based on the accumulation of multisystemic function declines and the increase in susceptibility to stressors during biological aging. The age-dependent senescence, the frailty-related stem cell depletion, chronic inflammation, imbalance of immune homeostasis, and the reduction of multipotent stem cells collectively suggest the rational hypothesis that it is possible to (partially) cure frailty with stem cells. This systematic review has included all of the human trials of stem cell therapy for frailty from the main electronic databases and printed materials and screened the closely related reviews themed on the mechanisms of aging, frailty, and stem cells, to provide more insights in stem cell strategies for frailty, one promising method to recover health from a frail status. To date, a total of four trials about this subject have been registered on clinicaltrials.gov. The use of mesenchymal stem cells (MSCs), doses of 100 million cells, single peripheral intravenous infusion, follow-up periods of 6-12 months, and a focus primarily on safety and secondarily on efficacy are common characteristics of these studies. We conclude that intravenous infusion of allogenic MSCs is safe, well tolerated, and preliminarily effective clinically. More preclinical experiments and clinical trials are warranted to precisely elucidate the mechanism, safety, and efficacy of frailty stem cell therapy.