Therapeutic effects of adipose-derived stem cells-based microtissues on erectile dysfunction in streptozotocin-induced diabetic rats.
Therapeutic effects of adipose-derived stem cells-based microtissues on erectile dysfunction in streptozotocin-induced diabetic rats.
复制标题
脂肪干细胞微组织对链脲佐菌素诱导的糖尿病大鼠勃起功能障碍的治疗作用
DOI：
10.4103/1008-682x.182817
复制
发表时间：
2017-01
影响因子：
2.9
通讯作者：
Xin ZC
中科院分区：
文献类型：
--
作者：
Zhou F;Hui Y;Xin H;Xu YD;Lei HE;Yang BC;Guan RL;Li M;Hou JQ;Xin ZC
本研究旨在探讨基于脂肪源性干细胞（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）的治疗作用。56只8周龄的Sprague-Dawley大鼠腹腔注射STZ (60 mg kg - 1)， 8周后，糖尿病大鼠随机接受海绵内（IC）注射磷酸缓冲液（PBS）、ADSCs或MTs， 8只正常大鼠同样接受IC注射PBS。采用悬挂滴法制备MTs，并对注射ADSC和mt的大鼠进行细胞追踪。治疗4周后，测定海绵体内压（ICP）、海绵体组织病理学改变（CC）及功能蛋白。采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）。注射MTs比注射ADSCs具有更高的滞留性，MTs改善了糖尿病大鼠的ICP、神经元一氧化氮合酶（nNOS）表达、平滑肌和内皮细胞含量，更好地改善了CC局部炎症。因此，我们的研究结果表明，IC注射MTs可以改善stz诱导的糖尿病大鼠的勃起功能和组织病理学变化，似乎比传统的ADSCs更有希望。潜在的机制涉及细胞潴留增加，伴有旁分泌因子的神经保护和抗炎行为。
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.