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

Abstract

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.

Mesenchymal Stem Cell Senescence and Rejuvenation: Current Status and Challenges

“…Auto-transplantation of MSCs has been shown to improve the function of MSCs extracted from patients (Sun, 2019). The same is urgently needed to improve MSC performance in vitro.…”

Application of mesenchymal stem cell therapy for aging frailty: from mechanisms to therapeutics

“…With the process of aging, frailty may be caused by multiple causes and contributors, including genetic and environmental factors 21 - 24 . To be more specific, genome instability 25 , DNA damage 26 , epigenetic alternations 27 , loss of proteostasis 28 , oxidative stress 29 , chronic inflammation 30 , mitochondrial dysregulation 31 , and stem cell exhaustion 24 , 32 are involved in the progression of aging frailty. These hallmarks are interconnected and ultimately lead to cellular senescence.…”

Inflammation, a Common Mechanism in Frailty and COVID-19, and Stem Cells as a Therapeutic Approach

“…Recently, randomized double blind studies showed that intravenous administration of allogeneic MSCs is safe, renders improved physical performance, and reduces inflammatory markers increased in frailty states. [42][43][44][45] In the first of these trails, 15 patients with mild to moderate frailty were treated with MSCs.…”