Zhou Feng, Hui Yu, Xin Hua, Xu Yong-De, Lei Hong-En, Yang Bi-Cheng, Guan Rui-Li, Li Meng, Hou Jian-Quan, Xin Zhong-Cheng
Molecular Biology Laboratory of Andrology Center, Peking University First Hospital, Peking University, Beijing 100034, China.
Department of Urology, First Affiliated Hospital of Soochow University, Soochow University, Suzhou 215006, China.
Asian J Androl. 2017 Jan-Feb;19(1):91-97. doi: 10.4103/1008-682X.182817.
This study aimed to explore the therapeutic effects of adipose-derived stem cells (ADSCs)-based microtissues (MTs) on erectile dysfunction (ED) in streptozotocin (STZ)-induced diabetic rats. Fifty-six 8-week-old Sprague-Dawley rats received intraperitoneal injection of STZ (60 mg kg-1 ), and 8 weeks later, the determined diabetic rats randomly received intracavernous (IC) injection of phosphate buffer solution (PBS), ADSCs, or MTs. Another eight normal rats equally got IC injection of PBS. MTs were generated with a hanging drop method, and the injected cells were tracked in ADSC- and MT-injected rats. Four weeks after the treatments, intracavernous pressure (ICP), histopathological changes in corpus cavernosum (CC), and functional proteins were measured. Rat cytokine antibody array was used to detect ADSCs or MTs lysate. The results showed that MTs expressed vascular endothelial growth factor (VEGF), nerve growth factor (NGF), and tumor necrosis factor-stimulated gene-6 (TSG-6). MTs injection had a higher retention than ADSCs injection and MTs treatment improved ICP, neuronal nitric oxide synthase (nNOS) expression, smooth muscle, and endothelial contents in diabetic rats, ameliorated local inflammation in CC better. Thus, our findings demonstrate that IC injection of MTs improves erectile function and histopathological changes in STZ-induced diabetic rats and appears to be more promising than traditional ADSCs. The underlying mechanisms involve increased cell retention accompanied with neuroprotection and anti-inflammatory behaviors of the paracrine factors.
本研究旨在探讨基于脂肪来源干细胞(ADSCs)的微组织(MTs)对链脲佐菌素(STZ)诱导的糖尿病大鼠勃起功能障碍(ED)的治疗效果。56只8周龄的Sprague-Dawley大鼠接受腹腔注射STZ(60 mg/kg),8周后,确诊的糖尿病大鼠随机接受海绵体内(IC)注射磷酸盐缓冲溶液(PBS)、ADSCs或MTs。另外8只正常大鼠同样接受IC注射PBS。采用悬滴法生成MTs,并在注射ADSCs和MTs的大鼠中追踪注射的细胞。治疗4周后,测量海绵体内压(ICP)、海绵体(CC)的组织病理学变化和功能蛋白。使用大鼠细胞因子抗体阵列检测ADSCs或MTs裂解物。结果显示,MTs表达血管内皮生长因子(VEGF)、神经生长因子(NGF)和肿瘤坏死因子刺激基因-6(TSG-6)。MTs注射比ADSCs注射具有更高的留存率,MTs治疗改善了糖尿病大鼠的ICP、神经元型一氧化氮合酶(nNOS)表达、平滑肌和内皮含量,更好地改善了CC中的局部炎症。因此,我们的研究结果表明,IC注射MTs可改善STZ诱导的糖尿病大鼠的勃起功能和组织病理学变化,并且似乎比传统的ADSCs更有前景。潜在机制包括细胞留存增加以及旁分泌因子的神经保护和抗炎行为。