Influence of Organismal Aging in Mesenchymal Stem Cell Therapy |Biomedgrid

Mesenchymal stem cells (MSCs) from several tissue sources have been investigated in clinical trials for multiple disorders, and mixed results from these trials have been documented [1], indicating that critical variables that can affect the therapeutic outcome remain to be defined. Organismal aging represents a potential impediment to stem cell therapy. Aged tissue often exhibits telomere shortening, increased Wnt signaling, and fibrosis [2,3], and may thus be more refractory to stem cell therapy. Accumulation of extracellular matrix (ECM) components, which invariably causes thickened lamina in aged tissue, can potentially impede the actions of the many growth/trophic factors secreted by the transplanted MSCs. Indeed, the aged heart often exhibits significant functional deteriorations contributed in part by cardiac stem cell senescence and lower capacity for angiogenesis [4]. Impaired HGF/c-Met and Delta/Notch signaling is also prominent in aged tissue [5].