(399d) Reprogramming Stem Cell Rejuvenation for Tissue Regeneration
During the course of our studies using mesenchymal stem cells (MSC) to engineer vascular grafts, we observed MSC originating from older donors suffer from limited proliferative capacity and significantly reduced myogenic differentiation potential. Notably, we developed a strategy to reverse the proliferation and differentiation potential of MSC from adult donors as well as to restore of ECM synthesis, actin polymerization and contractile function. In addition to MSC, we demonstrated that our strategy could ârejuvenateâ senescent skeletal muscle progenitor cells (SkMC) and identified molecular pathways that are involved in this process. Our strategy ameliorated important hallmarks of aging in SkMC including improvement in genomic integrity, reversal of histone epigenetic marks, increased cellular energetics and ultimately reversed muscle regeneration in vitro as well as in vivo, in a novel mouse model that we developed in our laboratory. In summary, our work demonstrates the potential of molecular engineering strategies to reverse the effects of cellular aging and restore the potential of adult stem cells for use in cellular therapies and tissue regeneration.