(178g) Mesenchymal Stem Cells for Vascular Tissue Engineering: Effects of Nanog and Oct4 Overexpression On Proliferation and Myogenic Differentiation

We demonstrated that bone marrow derived smooth muscle cells (BM-SMC) have high potential as an autologous cell source for vascular tissue engineering. However, recently we examined the effect of organismal aging on the properties of BM-SMC. We found that the proliferation potential and contractile function of BM-SMC declined with donor age. Recent studies suggested that overexpression of embryonic pluripotency transcription factors improved the quality of adult stem cells. Therefore, we proposed that overexpression of transcription factors such as Nanog or Oct4 may increase proliferation and differentiation potential of adult bone marrow derived mesenchymal stem cell (BM-MSC). To this end we used lentiviral vectors to overexpress Nanog or Oct4 in neonatal and adult BM-MSC and examined the effects on the properties of stem cells and tissue engineering vascular constructs (TEVs). Our results showed that Nanog or Oct4 overexpression significantly enhanced proliferation and clonogenic capacity of BM-MSC. In addition, TEVs constructed from Nanog+ adult BM-MSC demonstrated significantly higher level of vascular contractility as well as mechanical strength compared to their counterparts from control adult BM-MSC. On the other hand, Oct4 overexpression in neonatal or adult BM-MSC had a moderate effect on vascular contractility and negative effect on mechanical strength of TEVs. DNA microarray profiling is currently employed to identify the gene regulatory network that maybe activated by Nanog and determine potential targets that reverse aging effects in adult BM-MSC and the properties of the resulting TEVs.