Abstract 16528: The Recruitment of Neural Crest-Like Stem Cells Contributes to Vascular Regeneration
Introduction: Vascular grafts are widely used to replace diseased vessels. To facilitate the integration of vascular grafts into the host vasculature, it is critical to understand the mechanisms of remodeling upon the implantation of vascular grafts. However, this remodeling process is not well understood. In this study, we tested the hypothesis that endogenous stem cell homing participates in vascular regeneration.
Methods & Results: Nanofibrous vascular grafts were fabricated by using electrospinning technique. These scaffolds consist of fibers that mimic the porous micro- and nanostructure of native extracellular matrix components in the blood vessel wall. In the carotid artery bypass model, we found that at early time points (5d to 10d) after implantation, the grafts were populated with cells expressing neural crest stem cell (NCSC) marker Sox10 and early smooth muscle cell markers smooth muscle α-actin (SMA) and SM22α. However, these cells were negative for intermediate smooth muscle marker calponin-1 and mature smooth muscle marker smooth muscle myosin heavy chain. More interestingly, these cells could be isolated by explant culture of the implanted grafts and demonstrated the characteristics of NCSCs. Single cell cloning and differentiation assays showed that these cells were multipotent and could differentiate into neural lineages and mesenchymal lineages under specific induction conditions. The multipotency of the cells could be maintained in a special medium. When cultured in serum-containing medium for 1 month, these cells spontaneously differentiated into smooth muscle cells (SMCs). Consistently, in vivo studies showed that, after 1-month implantation, SMCs and matrix deposition were found in the surrounding neotissue of the grafts. After 3 months, more mature SMCs and matrix formed a compact smooth muscle layer.
Conclusions: Our findings suggest that the homing of endogenous neural crest-like stem cells contributes to the regeneration of blood vessels after vascular graft implantation. These stem cells can be isolated and expanded in vitro. The results from this study provide a rationale to recruit adult stem cells for in situ tissue engineering of vascular grafts, and will have significant impact on vascular tissue regeneration.
- © 2011 by American Heart Association, Inc.