Objective: The purpose of this review is to summarize the basic science literature related to chronic nerve injuries, and to then use this as the background to provide emerging insights into the promising role of cellular therapy for nerve injury repair.
Methods: The literature pertinent to the experimental and clinical aspects of chronic nerve injury was reviewed, as was emerging literature and our own recent experience in using cellular therapy to repair injured nerves.
Results: Peripheral nerves have the potential to regenerate axons and reinnervate end organs. Yet, outcome after peripheral nerve injury, even after nerve repair, remains relatively poor. The single most important quantitative contributor to poor motor recovery is chronic denervation of the distal nerve. Chronic denervation is common because of the often extensive injury zone that prevents any axonal outgrowth or (even if outgrowth occurs) the relatively slow rate of regeneration. As a consequence, the distal nerve remains chronically devoid of regrowing axons. In turn, prolonged denervation of Schwann cells (SCs) seems to be the critical factor that makes them unreceptive for axonal regeneration. Regenerative success was demonstrated when denervated SCs were replaced with healthy SCs cultured from a secondary nerve. This cell-replacement strategy is, however, limited in the clinical setting by the inability to obtain sufficient numbers of cells and the requirement for sacrifice of additional nerve tissue. We, along with several other groups, have therefore begun investigating stem cell therapies to improve the regenerative environment.
Conclusion: There are several avenues of stem cell-based approaches to peripheral nerve repair. One of these, skin-derived precursor cells, are easily accessible, autologous adult stem cells that can survive and myelinate in the peripheral nerve environment and become SC-like in their apparent differentiation.