Effects Of Adipose-derived Stem Cells-based Micro-tissues On Erectile Dysfunction In Diabetic Rats

Purpose: This study aimed to explore the therapeutic effects of adipose-derived stem cells(ADSCs)-based micro-tissues(MTs) on erectile dysfunction(ED) in streptozotocin(STZ) induced diabetic rats.Methods: ADSCs were isolated from 8-week-old Sprague-Dawley rats, MTs were generated with a hanging drop method. Fifty-six 8-week-old Sprague-Dawley rats received intraperitoneal injection of STZ(60mg/kg) and eight weeks later, the determined diabetic rats randomly received intracavernous injection of phosphate buffer solution(PBS), ADSCs or MTs. Another eight normal rats equally got intracavernous injection of PBS. Four weeks after the treatments, erectile functions of each group were measured as intracavernous pressure(ICP), cell retention and histopathological changes in corpus cavernosum were observed by immunofluorescence(IF), functional proteins of penis were measured by western blotting(WB). Rat cytokine antibody array and WB were used to detect ADSCs or MTs lysate, IF was used to identify MTs.Results: MTs expressed higher levels of vascular endothelial growth factor(VEGF), nerve growth factor(NGF), tumour necrosis factor-stimulated gene 6(TSG-6) and soluble intercellular cell adhesion molecule-1(sICAM-1) compared with ADSCs. MTs expressed CD105 but did not express CD31 or CD34. Diabetic rats showed significant decreases of ICP, alpha smooth muscle actin(α-SMA), von Willebrand factor(vWF), and neuronal nitric oxide synthase(nNOS) contents in penis. Both ADSCs and MTs injections could improve the erectile function of DMED rats, MTs injection had a higher retention than ADSCs injection and MTs treatment better improved ICP, nNOS expression, smooth muscle and endothelial contents in diabetic rats.Conclusions: Intracavernous injection of MTs improves erectile function and histopathological changes in streptozotocin-induced diabetic rats and appears to be more promising than traditional ADSCs. The underlying mechanisms involve increased cell retention accompanied with the paracrine behaviors of MTs.