ED 20. Neurotrophic effect of bone marrow mesenchymal stem cells for erectile dysfunction in diabetic rats

Introduction and Objective: Intracavernous injection of bone marrow derived mesenchymal stem cells (BM-MSCs) had been proved to be effective in improving erectile function and endothelium content within corpus cavernosum in type-1 diabetic rats. This study was designed to investigate the neurotrophic effect of BM-MSCs for type-1 diabetic rats.

Methods: Streptozocin induced type-1 diabetic rats were randomly divided into three groups: diabetic group (DM), BM-MSCs treated group (MSCs) and BM-MSCs conditioned medium treated group (Medium). At the 3d, 1w and 2w time points after BM-MSCs injection, 3 randomly selected rats in MSCs group were sacrificed and penile samples were harvested to detect BM-MSCs in penile tissue. Four weeks after intracavernous injection of BM-MSCs or BM-MSCs conditioned medium, intracavernous pressure (ICP) was assessed to evaluated the erectile function. Immunohistochemistry was used to track labeled BM-MSCs in penile tissue and to detect neuronal nitric oxide synthase (nNOS) and neurofilament (NF) positive fibers within penile dorsal nerve. Enzyme lined immunosorbent assay (ELISA) was used to measure the concentrations of vascular endothelial growth factor (VEGF), nerve growth factor (NGF) and brain derived neurotrophic factor (BDNF) in BMMSCs conditioned medium.

Results: BM-MSCs secreted detectable levels of VEGF, BDNF and NGF. Intracavernous injection of BM-MSCs improved erectile function in diabetic rats. The functional improvement was accompanied with promoted nNOS and NF positive nerve fibers within penile dorsal nerve in type-1 diabetic rats. Histological data revealed a time-dependent decrease in the number of BM-MSCs in the corpus cavernosum following injection. Furthermore, the beneficial effect of BM-MSCs was partially repeated by BM-MSCs conditioned medium.

Conclusions: Intracavernous injection of BM-MSCs is effective on improving nerve regeneration in diabetic rats. Paracrine effects of BM-MSCs are probably involved in the improvement.