IGF-1基因修饰骨髓间充质干细胞移植治疗糖尿病大鼠勃起功能障碍的研究

Erectile dysfunction (ED) in patients with diabetic mellitus (DM) have a strong negative effect on the quality of life of the sufferer and partner. We have confirmed insulin-like growth factor-1 (IGF-1) can promote the proliferation of corpous cavernous smooth muscle cells (CCSMCs) in vitro and improve the erectile function in diabetes rats in vivo. However, the long-term effects are limited. An effective and stable expression target gene and vector is the key for gene therapy of ED. The bone marrow derived mesenchymal stem cells (BM-MSCs) are adult stem cells that have been shown to be able to differentiate into various cell types. BM-MSCs can also secrete various growth factors which may attribute to the tissue recovery. Furthermore, BM-MSCs have nonimmunogenic and can survive for longer periods after autologous transplantation which is the ideal vector for cell-based gene therapy. Based on our previous study, in this study, we first modified the BM-MSCs with IGF-1, and then investigated the feasibility of intracavernous transplantation of the modified BM-MSCs for improving erectile function in streptozocin (STZ)-induced diabetic rats, and studied the possible mechanism of intracavernous transplantation. It may find a new target for gene therapy of ED and give a basement for the clinical trial.

糖尿病（DM）性勃起功能障碍（ED）严重影响患者和伴侣的生活质量。我们在前期研究中已经证实胰岛素样生长因子-1（IGF-1）能够促进阴茎海绵体平滑肌细胞（CCSMCs）的增殖；在糖尿病大鼠模型中可以短期提高大鼠勃起功能，但长期治疗效果欠佳，能否找到在体内长期稳定表达并具有很好治疗效果的靶基因和载体？骨髓间充质干细胞(BM-MSCs)是一种能够自我更新并具有向多种组织细胞分化潜能的成体干细胞，能够分泌多种促进组织修复的生长因子，同时BM-MSCs具有低免疫原性和存活时间较长等特性，适宜作为基因治疗的载体；本研究拟在前期研究基础之上对BM-MSCs进行基因修饰，探讨IGF-1基因修饰的BM-MSCs长期改善DM大鼠勃起功能的可行性，以期为DM ED的治疗提供一全新策略；同时探索其可能的分子机制，为确立ED治疗的新靶标提供科学依据，同时为进一步临床开发基因治疗药物奠定基础。

糖尿病（DM）性勃起功能障碍（ED）严重影响患者和伴侣的生活质量。我们在前期研究中已经证实胰岛素样生长因子-1（IGF-1）能够促进阴茎海绵体平滑肌细胞（CCSMCs）的增殖；在糖尿病大鼠模型中可以短期提高大鼠勃起功能，但长期治疗效果欠佳。骨髓间充质干细胞(BM-MSCs)适宜作为基因治疗的载体，因此本项目以BM-MSCs为载体细胞；对BM-MSCs进行基因修饰，即IGF-1体外转染BM-MSCs，探讨IGF-1基因修饰的BM-MSCs在1、3、6月不同时间点改善DM大鼠勃起功能的可行性，发现IGF-1基因修饰的BM-MSCs能够在移植3月时仍能够改善DM大鼠的勃起功能，为DM ED的治疗提供了一种新的策略；同时检测了各种分子指标，探索了其可能的分子机理，为开展临床实验奠定了良好的基础。