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

Abstract

Erectile dysfunction (ED) is a frequent complication of diabetes mellitus. The efficacy of common ED therapies is low for diabetes-associated ED. 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. 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. 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. 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. 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.