Intracavernous Transplantation of Bone Marrow-Derived Mesenchymal Stem Cells Restores Erectile Function of Streptozocin-Induced Diabetic Rats

Abstract

INTRODUCTION: Erectile dysfunction (ED) is a frequent complication of diabetes mellitus. The efficacy of common ED therapies is low for diabetes-associated ED. AIM: To explore the effects of transplantation of bone marrow-derived mesenchymal stem cells (BM-MSCs) on improving erectile function of streptozocin (STZ)-induced diabetic rats. METHODS: Male Sprague Dawley rats were injected either with STZ to induce diabetes or with citrate buffer as controls. Rat BM-MSCs were harvested and labeled with CM-DiI (Chloromethylbenzamido derivatives of 1,1'-dioctadecyl-3,3,3',3'-tetramethylindocarbocyanine perchlorate), and then transplanted into corporal cavernosum of STZ-induced diabetic rats. Four weeks after transplantation, all rats were analyzed for erectile function and penile histology. MAIN OUTCOME MEASURES: Erectile function was evaluated by the ratio between intracavernous pressure (ICP) and mean arterial pressure (MAP) during electrostimulation of cavernous nerve. Fate of transplanted BM-MSCs was identified using immunofluorescence staining. Smooth muscle and endothelium in corpora cavernosum were assessed using immunohistochemistry. RESULTS: After BM-MSCs transplantation, the ICP/MAP ratio was increased significantly compared with diabetic controls. Content of smooth muscle and endothelium in corporal cavernosa of BM-MSCs transplanted rats was significantly increased compared to diabetic controls. Immunofluorescence analysis demonstrated that CM-DiI-labeled BM-MSCs could stay in corporal cavernosa for at least 4 weeks and some of them expressed von Willebrand Factor, CD31, calponin, or α-smooth muscle actin, cells markers for endothelial cells or smooth muscle cells, respectively. CONCLUSION: Intracavernous transplantation of BM-MSCs had beneficial effects on erectile function of diabetic rats and increased the content of endothelium and smooth muscle in corporal cavernosum.