Adipose-Derived Stem Cells for Nerve Repair
Kacey G. Marra, PhD, Lizzie Y. Santiago, PhD, J. Peter Rubin, MD, Candace A. Brayfield, B.S., and Julio Clavijo-Alvarez, MD, PhD
INTRODUCTION:  Approximately 200,000 patients in the U.S. require surgical intervention for peripheral nerve injuries annually. Such nerve lesions result from trauma, tumors, and infections, or are adverse side effects of various surgeries. A challenge is that the axon length that must be recovered is not only the length of the gap, but also the length from the lesion to the innervated muscle, as end organs (such as muscle) may become atrophied before the axon can reinnervate the organs. Any manipulation that speeds axonal growth would have an immense impact on large gap peripheral nerve repair as it would improve the likelihood of serviceable motor and sensory control, which is the end goal of surgeons and patients.  Our approach to enhance long gap nerve regeneration involved the incorporation of adult adipose-derived stem cells within biodegradable conduits in a rat sciatic nerve defect model.¹
METHODS:  Human adipose-derived stem cells (ASCs) were isolated, characterized, then transplanted into the lumen of a polymeric nerve guide in a 6-mm unilateral sciatic nerve defect in athymic rats.  The three control groups for the study were biodegradable, polycaprolactone-based nerve conduit without cells, autograft, and empty defect.  Behavioral tests were performed every three weeks, and the sciatic functional index (SFI) was calculated based on measurements from the hindlimb prints.²  After 12 weeks, the nerve, right and left gastrocnemius muscles were removed and preserved for histological evaluation.
RESULTS:  ASCs survived transplantation for 12 weeks in the injured peripheral nerve.  No significant colocalization was observed between the immunostaining for glial fibrillary acidic protein (GFAP) and anti-human lamin A/C.  In comparison with the rats with untreated defects, a decrease in muscle atrophy was observed on those rats that received the autograft and the guide with cells as indicated by the gastrocnemius muscle weight ratio and the muscle fiber ratio.  Significant differences in SFI were observed three weeks post-injury between the rats in which the guide was left empty and those that received the guide with ASCs; however these differences were not observed at 12 weeks. 
CONCLUSIONS:  Full regeneration of the sciatic nerve occurred on rats that received the autograft, the guide, and the guide with ASCs; no regeneration was observed on any of the rats in which the defect was left untreated (empty defect).  The transplantation of ASCs promoted the formation of a more robust nerve as evidenced by histology, and the incorporation of ASCs produced a decrease in muscle atrophy.
REFERENCES:
1.         Santiago, L. Y., Clavijo, J., Brayfield, C., Rubin, J. P. and Marra, K. G. Delivery of adipose-derived precursor cells for peripheral nerve repair. Cell Transplantation, In Press. 2008.
2.         Clavijo, J. A., Nguyen, V. T., Santiago, L. Y., Doctor, J. S., Lee, W. P. A. and Marra, K. G. Comparison of biodegradable conduits in an aged rat sciatic nerve defect model. Plast. Reconstr. Surg., 119: 1839-1851, 2007.