Strategies for the Rejuvenation of Aged Muscle Stem Cells

Abstract

A decline in the regenerative capacity of adult stem cells during aging is well documented. We investigated whether reversing the aged phenotype is possible in muscle‐derived stem cells (MDSCs). Previous studies have demonstrated that MDSC‐based cell therapies are efficacious for muscle, bone, cartilage, and cardiac injury. We have isolated MDSCs from aged (24 month old) and young (14 day old) wild type (WT) mice. We screened a number of compounds for their effect on aged stem cell proliferation and myogenic differentiation. Treatment with an inhibitor of nuclear factor kappa B (NF‐kB) rescued the myogenic capacity of aged MDSCs. This led us to hypothesize that NF‐kB activation reversibly suppresses the function of aged MDSCs. To investigate this further, we isolated MDSCs from 30 month old mice haploinsufficient for p65 (p65+/−). Our results have found that aged p65+/− MDSCs are myogenic in vitro and have a higher resistance to oxidative stress than WT cells. Currently, we are comparing the muscle regeneration potential of aged WT and p65+/− MDSCs following injection into injured skeletal muscle of aged mice. Our results suggest that MDSC “aging” may be reversible, and that pharmacologic targeting of pathways such as NF‐kB may enhance the efficacy of cell therapies in aging patients. This work was supported by the Henry J. Mankin Endowed Chair for Orthopaedic Research and the Hirtzel Foundation.Grant Funding Source : Department of Defense