Induced pluripotent stem cells (iPSCs) have tremendous potential for regenerative medicine applications. Here we use peripheral nerve regeneration as a model to address the fundamental issues of using iPSCs and their derivatives for therapies. Specifically, we used integration-free iPSCs for our studies because this type of iPSCs has potential for clinical applications. We derived and characterized neural crest stem cells (NCSCs) from integration-free iPSCs, and demonstrated that these NCSCs can differentiate into a variety of cell types, including Schwann cells. We delivered NCSCs into nerve conduits to treat peripheral nerve injuries, and performed functional studies, electrophysiology analysis and histological analysis. Ongoing studies suggest that the transplantation of iPSC-NCSCs accelerate nerve regeneration. To investigate the interactions of transplanted stem cells with endogenous neural progenitors, we isolated and characterized endogenous progenitors from injured nerves, which will be used for mechanistic studies. In addition, we engineered the chemical components and the structure of nerve conduits, and developed and characterized hydrogels that could be used to deliver neurotrophic factors and minimize scar formation. The roles of neurotrophic factors, transplanted/endogenous stem cells and matrix for stem cell delivery will be investigated.