(145f) Effect of Organismal Aging on Bone Marrow Derived Smooth Muscle Progenitor Cells

Recently we demonstrated that functional smooth muscle progenitor cells can be derived from bone marrow (BM-SMPCs) and have high potential as an autologous cell source for vascular tissue engineering. However, normal cell function and turnover frequency decline with aging so that understanding the effect of aging on cell phenotype and function is very important. To address this question, we used a smooth muscle alpha actin promoter (SMaA) driving expression of EGFP to isolate BM-SMPCs from neonatal (n=3) or adult sheep (n=3) and examined the effect of animal aging on the properties of stem cells and tissue engineering vascular constructs. Our results showed that the proliferation capacity and clonogenic ability of neonatal cells were significantly higher than adult BM-SMPC. In addition, tissue engineered blood vessels (TEVs) constructed from neonatal cells demonstrated significantly higher level of receptor and non-receptor mediated vascular contractility as well as mechanical strength compared to TEVs from adult BM-SMPCs. Differential gene expression profiling using quantitative real-time PCR showed that adult BM-SMPCs expressed higher levels of matrix metalloproteases but neonatal cells expressed significantly higher levels of extracellular matrix molecules e.g. tropoelastin. These results are currently extended to obtain a comprehensive gene expression profile as a function of aging and determine potential strategies to reverse these effects in adult BM-SMPCs. Ultimately these efforts may enhance the potential of bone marrow mesenchymal stem cells for tissue regeneration.