Bone Marrow-Derived Mesenchymal Stem Cells Enhance Cryopreserved Trachea Allograft Epithelium Regeneration and Vascular Endothelial Growth Factor Expression

Abstract

Epithelium regeneration and revascularization of tracheal implants are challenging issues to be solved in tracheal transplantation research. Bone marrow-derived mesenchymal stem cells (BMSCs) can migrate to the damaged tissue and promote functional restoration. Here, we applied intravenous transplantation of BMSCs combined with a cryopreserved allograft to investigate the role of BMSCs in enhancing implant survival, tracheal epithelium regeneration and revascularization. After transplantation with cryopreserved allografts, PKH-26 labeled 3 to 5 passage BMSCs were injected into recipient rats through the tail vein. Rats in the control groups were injected with a comparable amount of phosphate-buffered saline. We observed the histology of the tracheal allograft and measured vascular endothelial growth factor (VEGF) protein levels in the epithelium to evaluate the effect of BMSCs on epithelium regeneration and revascularization. Histologic observation of the rats from the BMSCs injection groups showed that the tracheal lumen was covered by pseudostriated ciliated columnar epithelium. The cartilage structure was intact. There were no signs of denaturation or necrosis. PKH-26 labeled BMSCs migrated to the implant site and exhibited red fluorescence, with the brightest red fluorescence at the anastomotic site. VEGF protein levels in the allograft epithelium of the BMSCs injection group were higher than the levels in the phosphate-buffered saline injection group. Our results indicate that given systemic administration, BMSCs may enhance epithelium regeneration and revascularization by upregulating VEGF expression.