Department of Urology, Wuxi No. 3 People's Hospital, Wuxi, China.
Department of Urology, Second Affiliated Hospital of Nanjing Medical University, Nanjing, China.
Can J Diabetes. 2017 Jun;41(3):312-321. doi: 10.1016/j.jcjd.2016.11.002. Epub 2017 Feb 22.
Diabetic cystopathy (DCP), characterized by peripheral neuropathy-associated bladder dysfunction, is a common urinary complication in patients with diabetes (~80%). Bone marrow mesenchymal stem cell (BMMSC) transplantation, a new and emerging regenerative therapy, provides a curative option for DCP. However, the application of this therapy is limited by the low survival rate and engraftment of transplanted stem cells. This study was undertaken to determine whether integrin-linked kinase (ILK) overexpression would improve stem cell survival and engraftment after BMMSC transplantation.
Diabetes was induced in rats by injection of streptozotocin. ILK expression was detected by qRT-PCR and Western blot. Bladder function was measured by urodynamic analyses. Smooth-muscle regeneration and vascularization were evaluated by immunohistochemistry staining.
ILK overexpression by adenovirus promotes proliferation of BMMSCs in vitro. ILK overexpression enhanced the ability of BMMSCs to decrease the volume threshold for micturition and residual urine in the rats with diabetes. The contractile response of bladder strips, tissue structure of bladder and smooth-muscle regeneration/vascularization were also improved in the rats receiving ILK-modified BMMSCs.
Our data highlight the clinical potential of transplantation of gene-modified BMMSCs in the treatment of DCP, thereby serving as a rapid and effective first-line strategy to cure the bladder dysfunction resulting from long-term diabetes.
糖尿病性膀胱病（DCP）的特征是周围神经病变相关的膀胱功能障碍，是糖尿病患者常见的尿路并发症（约 80%）。骨髓间充质干细胞（BMMSC）移植作为一种新兴的再生治疗方法，为 DCP 提供了一种治疗选择。然而，这种治疗方法的应用受到移植干细胞存活率和植入率低的限制。本研究旨在确定整合素连接激酶（ILK）过表达是否会提高 BMMSC 移植后的干细胞存活率和植入率。
通过链脲佐菌素注射诱导大鼠糖尿病。通过 qRT-PCR 和 Western blot 检测 ILK 表达。通过尿动力学分析测量膀胱功能。通过免疫组织化学染色评估平滑肌再生和血管生成。
腺病毒过表达 ILK 促进 BMMSCs 的体外增殖。ILK 过表达增强了 BMMSCs 降低糖尿病大鼠排尿量阈值和残余尿量的能力。接受 ILK 修饰的 BMMSCs 的大鼠的膀胱条带的收缩反应、膀胱组织结构以及平滑肌再生/血管生成也得到了改善。
我们的数据强调了基因修饰的 BMMSCs 移植在治疗 DCP 中的临床潜力，因此成为治疗长期糖尿病引起的膀胱功能障碍的快速有效一线策略。
