Bone marrow derived mesenchymal stem cells from aged mice have reduced wound healing, angiogenesis, proliferation and anti-apoptosis capabilities

Abstract

Decline in the function of stem cells with age, such as other cells of the body, results in an imbalance between loss and renewal. Increasing age of the donor thus diminishes the effectiveness of MSCs (mesenchymal stem cells) transplantation in age-related diseases. The clinical use of stem cell therapies needs autologous stem cell transplantation; it is essential therefore to study the repair ability and survivability of cells before transplantation. Bone marrow derived MSCs possess multi-lineage differentiation potential, but aging adversely affects their therapeutic efficacy. MSCs from young (2-3 months) and aged (23-24 months) GFP (green fluorescent protein)-expressing C57BL/6 mice were isolated and their regenerative potential was assessed in vitro. Real-time RT-PCR (reverse transcriptase-PCR) showed significantly higher expression of Sirt1 in MSCs isolated from young than older animals. Down-regulation of VEGF (vascular endothelial growth factor), SDF-1 (stromal-cell-derived factor 1), AKT (also known as protein kinase B) and up-regulation of p53, p21, Bax and p16 occurred in aged cells. Tube formation, wound healing and proliferative abilities of the young MSCs were better than the aged MSCs. The results suggest that age-related increased expression of apoptotic and senescent genes, with concomitant decrease in Sirt1 gene expression, inhibits to some extent stem cell functioning.