UC Berkeley

The thesis includes two parts: (1) the role of stem cells in nerve regeneration, and (2) the role of stem cells in the development of vascular diseases. The use of stem cells has promising potential for the fields of tissue engineering and regenerative medicine, which relies on precise control of cell proliferation and differentiation by cellular, biochemical and biophysical cues. For cell therapy in tissue regenerative applications, the specific differentiation state of implanted cells must be optimized to control cell fate, viability, potency and safety in vivo. In this dissertation, we investigate the therapeutic effect of induced pluripotent stem cell-derived neural crest stem cells (iPSC-NCSCs) at various differentiation stages and mesenchymal progenitor cells (MPCs) on peripheral nerve regeneration. Transplantation of NCSCs has better outcomes of motor nerve recovery and muscle reinnervation by Schwann cell differentiation in vivo and paracrine signaling, whereas transplantation of MPCs fails to promote functional nerve regeneration. This study provides an insight into the selection of stem cells during tissue regeneration, and has broad impact on the strategic design of cell therapy for tissue engineering. It is generally accepted that the phenotypical de-differentiation of smooth muscle cells (SMCs) has an important role in the development of vascular diseases. Here we identify a population of SOX10+ vascular stem cells (VSCs) that can be isolated from human blood vessel wall and are able to differentiate into cell types of neural lineages and mesenchymal lineages in vitro. SOX10+ cells can be identified in both normal and diseased blood vessels, and some of these cells are positive for osteogenic and adipogenic markers, suggesting that the differentiation of VSCs in blood vessel in vivo can contribute to vascular diseases. In addition, in situ polymerase chain reaction proximity ligation assay (ISPCR-PLA) shows that some of the SOX10+ cells are derived from SMCs. Further investigation of these cells will help us understand the mechanism of vascular pathogenesis and potential therapeutic target of vascular diseases. The work in this dissertation demonstrates the important role of stem cells in tissue regeneration and diseases, which may lead to wide applications in stem cell biology, tissue engineering and regenerative medicine.