Transplantation of bone marrow-derived mesenchymal stem cells expressing elastin alleviates pelvic floor dysfunction.
Transplantation of bone marrow-derived mesenchymal stem cells expressing elastin alleviates pelvic floor dysfunction.
复制标题
移植表达弹性蛋白的骨髓间充质干细胞可缓解盆底功能障碍。
DOI：
10.1186/s13287-016-0308-1
复制
发表时间：
2016-04-05
影响因子：
7.5
通讯作者：
Hua X
中科院分区：
文献类型：
--
作者：
Jin M;Chen Y;Zhou Y;Mei Y;Liu W;Pan C;Hua X
骨盆底功能障碍（PFD）是一组临床疾病，包括压力性尿失禁（SUI）和盆腔器官脱垂（POP）。胶原和弹性蛋白在盆腔结缔组织中的代谢异常与SUI和POP有关，为了重建胶原和弹性蛋白正常分布的结缔组织，我们将弹性蛋白转导至骨髓间充质干细胞（BMSC）。表达弹性蛋白的BMSC然后使用bFGF分化成纤维细胞，其产生胶原蛋白和弹性蛋白。为了实现bFGF的持续释放，我们将bFGF配制在聚（乳酸-共-乙醇酸）（PLGA）纳米颗粒（NP）中。在7天的体外细胞培养系统中，当不施用额外的bFGF时，初始的PLGA负载的bFGF NP诱导从表达弹性蛋白的BMSC产生胶原蛋白和弹性蛋白的延长。在体内，共注射PLGA负载的bFGF NP和表达弹性蛋白的BMSCs到PFD大鼠中显着改善尿动力学测试的结果。总之，这些结果提供了一个有效的模型，结缔组织工程使用BMSC和可注射的PLGA加载的生长因子。我们的研究结果提供了多学科方法的第一例，结合干细胞和纳米颗粒技术，用于治疗PFD。
Pelvic floor dysfunction (PFD) is a group of clinical conditions including stress urinary incontinence (SUI) and pelvic organ prolapse (POP). The abnormality of collagen and elastin metabolism in pelvic connective tissues is implicated in SUI and POP. To reconstitute the connective tissues with normal distribution of collagen and elastin, we transduced elastin to bone marrow-derived mesenchymal stem cells (BMSC). Elastin-expressing BMSCs were then differentiated to fibroblasts using bFGF, which produced collagen and elastin. To achieve the sustained release of bFGF, we formulated bFGF in poly (lactic-co-glycolic acid) (PLGA) nanoparticles (NP). In an in vitro cell culture system of 7 days, when no additional bFGF was administrated, the initial PLGA-loaded bFGF NP induced prolonged production of collagen and elastin from elastin-expressing BMSCs. In vivo, co-injection of PLGA-loaded bFGF NP and elastin-expressing BMSCs into the PFD rats significantly improved the outcome of urodynamic tests. Together, these results provided an efficient model of connective tissue engineering using BMSC and injectable PLGA-loaded growth factors. Our results provided the first instance of a multidisciplinary approach, combining both stem cell and nanoparticle technologies, for the treatment of PFD.