The Use and Delivery of Stem Cells in Nerve Regeneration: Preclinical Evidence and Regulatory Considerations

Outcomes following peripheral nerve injury remain poor despite the regenerative capacity displayed by the peripheral nervous system. Current therapies are limited and do not provide satisfactory functional recovery in a multitude of cases. Biomaterials have decreased the need for nerve autograft across small nerve gaps in small-caliber nerves, but the lack of a cellular substrate presents a limiting factor to the effectiveness of this therapy. Schwann cells are the supportive cells in the peripheral nervous system and play an integral role in the physiological response and regeneration following nerve injury. Limitations to autologous Schwann cells include donor site morbidity during harvesting, limited expansion capability, and finite source. Stem cells are multipotent or pluripotent cells with self-renewing capabilities that show promise to improve functional recovery following nerve injury. Differentiation of stem cells into supportive Schwann cells could provide additional trophic support without the disadvantages of autologous Schwann cells, providing an avenue to improve existing therapies. A variety of stem cells have been evaluated in animal models for this clinical application; the current options, along with their clinical feasibility, are summarized in this article.