AB76. Adipose-derived stem cells improve erectile function through secretion of growth factor in aged rat

Introduction & objectives: Adipose-derived stem cells (ADSCs) have been recently considered promising therapy for erectile dysfunction (ED). However, the mechanism of ADSCs-based therapy remains to be elucidated. The aim of this study was to determine whether transplantation of ADSCs was capable of resolving aging-related ED, and to investigate its underlying mechanisms.

Materials & methods: Hepatocyte growth factor (HGF), angiopoitein-1 (ANG-1), angiopoitein-2 (ANG-2), insulin-like growth factor (IGF-1), vascular endothelial growth factor (VEGF) and basic fibroblast growth factor (bFGF) secreted by ADSCs were assessed in vitro. Furthermore, the protective effects of VEGF and bFGF secreted by ADSCs were evaluated in vitro by means of neutralization of VEGF, bFGF or both using CCK-8. Sixteen 24-month-old male Sprague-Dawley rats were used for comparative analysis of 2-week treatment regiments with CM-DiI labeled ADSCs or PBS. Eight additional 5-month-old rats were used as young rats group. At 2-week post-transplantation, all the rats were analyzed for erectile function, cavernous VEGF and bFGF levels, and penile histology. The VEGF and bFGF levels of ADSCs-conditioned medium and penile tissues were determined by an enzyme-linked immunosorbent assay (ELISA). The ratio of maximal intracavernous pressure (ICP) to mean arterial blood pressure (MAP) was measured to evaluate erectile function. Immunofluorescence staining was used to evaluate the number of ADSCs, and the contents of cavernous smooth muscle and endothelium.

Results: ADSCs could secrete a large amount of VEGF and bFGF in culture medium compared to basal medium (P<0.05). Rat corpus cavernosum smooth muscle cells (CCSMCs) grew more slowly due to oxidative stress. However, conditioned DMEM of ADSCs played a protection role. Neutralization of VEGF, or both of VEGF and bFGF could significantly attenuate the effect. bFGF played a less important role in the protective effect. Compared to the young rats, the untreated aged rats showed significantly lower Max ICP/MAP (P<0.05) and ADSCs treatment significantly increased the ratio (P<0.05). Immunofluorescence staining demonstrated that there was only a small number of CM-DiI labeled ADSCs found in corpus cavernosum. The corpus cavernosum of untreated aged rats showed decreased VEGF and bFGF levels, and the contents of cavernous smooth muscle and endothelium compared to young rats (P<0.05). ADSCs treatment partially normalized these alterations (P<0.05).

Conclusions: ADSCs treatment may improve aging-related ED partially through secretion of VEGF and bFGF.

Keywords: Adipose-derived stem cells; erectile dysfunction (ED); vascular endothelial growth factor (VEGF); basic fibroblast growth factor (BFGF)