Improvement of erectile dysfunction using endothelial progenitor cells from fetal cerebral vasculature in the cavernous nerve injury of rats

BACKGROUND: Because of limited differentiation to endothelium from mesenchymal stem cells, it has been strongly recommended to use endothelial progenitor cells for the regeneration of the damaged endothelium of corpora cavernosa. This study was performed to investigate the immortalized human cerebral endothelial cells and their capability for repairing erectile dysfunction in a rat model of cavernous nerve injury. Circulating endothelial progenitor cells were isolated from human fetal brain vasculature at the periventricular region of telencephalic tissues. Over 95% of CD 31-positive cells were sorted and cultured for 10 days. Human cerebral endothelial progenitor cells were injected into the cavernosa of rats with cavernous nerve injury. Erectile response was then assessed. In in vivo assays, rats were divided into three groups: group 1, sham operation: group 2, bilateral cavernous nerve injury: and group 3, treatment with human cerebral endothelial cells after cavernous nerve injury. RESULTS: Established immortalized circulating endothelial progenitor cells showed expression of human telomerase reverse transcriptase transcript by RT-PCR. They also showed the expression of vascular endothelial growth factor, von Willebrand factor, vascular endothelial growth factor receptor, and CD31, cell type-specific markers for endothelial cells by RT-PCR. In in vitro angiogenesis assays, they demonstrated tube formation that suggested morphological properties of endothelial progenitor cells. In in vivo assays, impaired erectile function of rat with cavernous nerve injury recovered at 2, 4, and 12 weeks after transplantation of human cerebral endothelial cells into the cavernosa. CONCLUSIONS: Telomerase reverse transcriptase-circulating endothelial progenitor cells from fetal brain vasculature could repair erectile dysfunction of rats with cavernous nerve injury.