Uncultured adipose-derived regenerative cells promote peripheral nerve regeneration

We examined whether or not peripheral nerves can be regenerated using uncultured adipose-derived regenerative cells (ADRCs). We also searched for humoral factors that might promote the proliferation or migration of Schwann cells. Thirty rats were randomly assigned to three groups. A 10 mm sciatic nerve defect was bridged using a silicon tube filled with physiological saline (control group), type I collagen gel (collagen group), and a mixture of ADRCs and type I collagen gel (ADRC group). The regenerated tissues were studied two weeks after surgery. Continuity of regenerated tissue was observed in all rats in the control group and the ADRC group. In the collagen group, only two rats had a bridge of thin tissue, which was barely visible macroscopically. Protein gene product 9.5 staining confirmed significantly faster regeneration in the ADRC group. The distributions of the PKH-26 positive areas and the S-100 protein positive areas were different, suggesting that the transplanted cells had not differentiated into Schwann cells. In real-time RT-PCR, neuregulin-1 (Neu-1) and vascular endothelial growth factor A (VEGFA) expression were detected in uncultured ADRCs before transplantation. The regenerated tissue in the ADRC group had higher levels of Neu-1 and VEGFA expression than the control group. ADRCs promote peripheral nerve regeneration. The mechanism does not involve the differentiation of transplanted cells into Schwann cells, but probably involves the secretion of some type of humoral factor such as Neu-1 or VEGFA that promotes the proliferation or migration of Schwann cells.