Tissue engineering of Schwann cells (SCs) can serve a number of purposes, such as in vitro SC-related disease modeling, treatment of peripheral nerve diseases or peripheral nerve injury, and, potentially, treatment of CNS diseases. SCs can be generated from autologous stem cells in vitro by recapitulating the various stages of in vivo neural crest formation and SC differentiation. In this review, we survey the cellular and molecular mechanisms underlying these in vivo processes. We then focus on the current in vitro strategies for generating SCs from two sources of pluripotent stem cells, namely embryonic stem cells (ESCs) and induced pluripotent stem cells (iPSCs). Different methods for SC engineering from ESCs and iPSCs are reviewed and suggestions are proposed for optimizing the existing protocols. Potential safety issues regarding the clinical application of iPSC-derived SCs are discussed as well. Lastly, we will address future aspects of SC engineering.

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Induced pluripotent stem cells (iPSCs) are promising candidates for the study of disease models as well as for tissue engineering purposes. Part of a strategy to develop safe reprogramming technique is reducing the number of exogenous reprogramming factors. Some cells types are more prone to reprogramming than others. iPSC induction with less reprogramming factors has been described in cells with endogenous expression levels of pluripotency genes, such as neural stem cells. Because multipotent neural crest stem cells (NCSCs) from mammalian hair follicle bulges also express pluripotency genes, we argued that this property would facilitate reprogramming of hair follicle bulge NCSCs and could substitute for the use of exogenous reprogramming factors. Although we confirmed the expression of pluripotency genes in hair follicle bulge cells, our results show that these cells do require a full set of reprogramming factors for iPSC induction. Hair follicle bulge-derived iPSCs were created with efficiencies similar to fibroblasts. We conclude that high endogenous levels of pluripotency factors are no guarantee for facilitated induction of pluripotency.

Nerve guides seeded with Schwann cells (SCs) promote axonal regeneration in peripheral nerve lesions. We examined the applicability of bioluminescent imaging (BLI) for monitoring the fate of SCs in nerve guides after implantation. Rat SCs were transfected with the firefly luciferase (Fluc) gene and subsequently seeded in nerve guides, which were implanted subcutaneously in rats. In vivo bioluminescence of transfected SCs (Fluc-SCs) was assessed with a BLI system. Scans were validated ex vivo using immunocytochemistry and electron microscopy. We found that BLI enables longitudinal in vivo monitoring of Fluc-SCs, given that proper access of luciferin to the cells is assured.