Effect of Recombinant Human BDNF Gene Therapy on the Nerve Regeneration in Rat Sciatic Nerve Transection

Abstract

surgical procedure currently used for repairing facial nerve defects caused by traffic accidents or malignant tumor resections (Kumar et al, 2002). A number of recent studies have shown the effectiveness of tubulation as an alternative therapy to that of nerve autografting for peripheral nerve gaps (Matsumoto et al, 2000). For large peripheral nerve defects, tubulation alone is limited to nerve regeneration. It has been reported that tubulation using brain-derived neural progenitor cells or Schwann cells promotes nerve regeneration (Murakami et al, 2003). However, use of these neural cells from other neural tissues has potentially serious clinical complications along with ethical considerations. Therefore, we focused on the use of dental pulp as a new cell source for such artificial nerves. Dental pulp is derived from the neural crest, included fibroblasts, and Schwann and stem cells. It is assumed that these cells have an important role in peripheral nerve regeneration. Therefore, we investigated whether transplanted dental pulp cells in a facial nerve gap promoted nerve repair. Materials and Methods: Adult Sprague-Dawley (SD) rats were anesthetized by isoflurane using an original nasal mask. A 7-mm defect was prepared in the buccal branch of the facial nerve. Dental pulp cells were isolated from adult SD rat maxillary incisors containing a transgene-expressing green fluorescent protein (GFP). The defect was bridged with a 10-mm silicone tube filled with GFP-positive dental pulp cells (1.0 105) embedded in type I collagen gel. Both the proximal and distal stump of the nerve was inserted about 1.0-mm into the tube and connected with 2 sutures of 9-0 nylons under microscopy. Method of Data Analysis: The regenerated nerve was evaluated by immunohistologic study. Results: 14 days after surgery, a GFP-positive regenerated nerve was observed in the silicone tube. The regenerated nerve included Tuj1-positive axons and RECA1positive vessels. These results suggested that transplanted dental pulp cells may differentiate into supportive cells and may support axonal regeneration. Conclusion: When dental pulp cells are transplanted into a large peripheral nerve defect, they may contribute to the promotion of axonal regeneration. Dental pulp may be a viable source of easily obtainable cells for potential use in facial nerve regeneration.