AB157. Treatment of diabetic erectile dysfunction by using endothelial progenitor cells genetically modified by human telomerase reverse transcriptase

Objective: Erectile dysfunction (ED) is one of the most common complications of diabetes mellitus (DM). Under the background that effectivity of treatments for diabetic ED are quite poor, stem cell therapy is emerging a useful method. The aim of this study is to evaluate the possibility and mechanism of treatment of diabetic ED with endothelial progenitor cells (EPCs) genetically modified by human telomerase reverse transcriptase (hTERT).

Methods: Rat EPCs were isolated and transfected with hTERT (EPCs-hTERT). The paracrine characters and resistance to oxidative stress of EPCs-hTERT was determined in vitro. Thirty SD male rats were divided into five groups: diabetic ED rats, diabetic ED rats treated with EPCs, diabetic ED rats treated with EPCs-control, diabetic ED rats treated with EPCs-hTERT, normal control rats. Diabetes was induced by intraperitoneal injection of streptozotocin. After 8 weeks, diabetic ED rats were selected by apomorphine (APO) test. After injection of EPCs for 2 weeks, intracavernosal pressure (ICP) was measured by means of electrical stimulation for each group. Concentration of growth factors, the amount of EPCs and endothelium/smooth muscle content were evaluated in vivo.

Results: EPCs-hTERT showed stable expression of hTERT at the level of, mRNA and protein for more than 40 passages. EPCs-hTERT could paracrine more VEGF, HGF and bFGF. EPCs’ ability of resistance to oxidative stress was dramatically improved by tranfection of hTERT. ICP/mean arterial pressure (MAP) ratio induced by electrical stimulation in diabetic ED treated with EPCs-hTERT was markably higher than diabetic ED rats treated with EPCs or EPCs-control. Immunofluorescence demonstrated that more cells survived in penile tissues after implantation of EPC-hTERT. More growth factors were detected, and the endothelium/smooth muscle content was increase in penile tissues.

Conclusions: The paracrine effect and resistance to oxidative stress of EPCs-hTERT contributed to the improvement of erection of diabetic ED rats.

Keywords: Diabetes mellitus (DM); erectile dysfunction (ED); human telomerase reverse transcriptase (hTERT); endothelial progenitor cells (EPCs)