Acceleration of Sensory Neural Regeneration and Wound Healing With Human Mesenchymal Stem Cells in Immunodeficient Rats

¹ Division of Plastic and Reconstructive Surgery; Department of Developmental and Reconstructive Medicine Nagasaki University, Graduate School of Biomedical and Sciences 1-7-1 Sakamoto machi, Nagasaki, 8528501, Japan
² Division of Plastic and Reconstructive Surgery; Department of Developmental and Reconstructive Medicine, Nagasaki University, Graduate School of Biomedical and Sciences, 1-7-1 Sakamoto machi, Nagasaki, 8528501, Japan
³ Division of Anatomy and Neurobiology; Department of Developmental and Reconstructive Medicine, Nagasaki University, Graduate School of Biomedical and Sciences, 1-7-1 Sakamoto machi, Nagasaki, 8528501, Japan

^* To whom correspondence should be addressed. E-mail: akitas{at}hf.rim.or.jp.

	Abstract

The sensory nerve is highly involved in lower extremity wound healing. In diabetic and vascular diseases, impaired nerve function and blood flow delay wound healing. Tissue regeneration using adult stem cells is a targeted therapeutic modality in disorders of nerve and blood supply. Effective delivery using an autologous vascularized fascial flap as a vehicle of stem cells leads to severed sensory nerve recovery, local tissue blood flow and wound healing. Human mesenchymal stem cells (hMSCs) were transfected with green fluorescent protein (GFP) cDNA and tested for efficiency and proliferation in vitro. The nude rat model with femoral vessel and saphenous nerve severance, and ligation was wrapped with a vascularized epigastric flap for GFP-hMSC, fibroblast growth factor-2 (FGF-2) or a combination of both after 2 weeks. Maximum nerve conduction velocity recovered to 70% of the pre-surgical level in the GFP-hMSC and FGF-2-treated group at 2 weeks. Blood flow and nerve conduction velocity were positively correlated at 1 week. Wound healing in the ipsilateral paw had significantly improved by 1 week. Histologically, blood vessels and nerves are very organized, and regenerated neuron immunoreactivity of GAP-43 and a nerve regrowth marker of S-100 were remarkable in the hGFP-hMSC and FGF-2-treated group at 2 weeks; therefore, sensory nerve regeneration, blood flow and wound healing were improved by the administration of stem cells and FGF-2 via a vascularized flap. This may be implicated in clinical denervated and reduced circulation tissue wound healing.