Mesenchymal stem cells and their secretome partially restore nerve and urethral function in a dual muscle and nerve injury stress urinary incontinence model
Mesenchymal stem cells and their secretome partially restore nerve and urethral function in a dual muscle and nerve injury stress urinary incontinence model
复制标题
DOI：
10.1152/ajprenal.00510.2014
复制
发表时间：
2015-01-15
影响因子：
4.2
通讯作者：
Damaser, Margot S.
中科院分区：
文献类型：
--
作者：
Deng, Kangli;Lin, Dan Li;Damaser, Margot S.
分娩会损伤肌肉和神经，导致尿失禁。骨髓间充质干细胞(MSCs)或其分泌体的全身应用可为这一复杂的多部位损伤提供治疗优势。我们研究了从细胞培养中收集的间充质干细胞或其分泌体是否有助于从模拟分娩损伤中恢复。年龄匹配的雌性SD大鼠接受阴部神经挤压和阴道扩张(PNC+VD)，并单次静脉注射200万MSCs或生理盐水。对照组接受假损伤和静脉注射生理盐水。另一些大鼠接受PNC+VD和一次腹腔注射(IP)经MSCs条件的浓缩液(CCM)或浓缩对照液(CM)。对照组接受假损伤和IP CM。伤后3wk用漏点压(LPP)和阴部神经感觉支电位(PNSBP)测定尿路和神经功能。采用盲法对尿路和阴部神经解剖进行定性评价。计量资料分析采用单因素方差分析和Holm-Sidak后置检验，P<；0.05显示有显著差异。与假手术组比较，PNC+VD+生理盐水或CM组大鼠LPP和PNSBP均显著降低，而MSC和CCM组大鼠LPP和PNSBP无明显变化。PNC+VD后，尿路弹性纤维密度增加，且有方向性改变，其中MSC或CCM组弹性纤维密度增加幅度更大。PNC+VD组阴部神经束密度较低，形状不规则，MSC或CCM组病理改变较轻。MSC和CCM在PNC+VD后具有相似的保护作用，提示MSCs在这种肌肉和神经双重损伤中通过分泌发挥作用。
Childbirth injures muscles and nerves responsible for urinary continence. Mesenchymal stem cells (MSCs) or their secretome given systemically could provide therapeutic benefit for this complex multisite injury. We investigated whether MSCs or their secretome, as collected from cell culture, facilitate recovery from simulated childbirth injury. Age-matched female Sprague-Dawley rats received pudendal nerve crush and vaginal distension (PNC + VD) and a single intravenous (iv) injection of 2 million MSCs or saline. Controls received sham injury and iv saline. Additional rats received PNC + VD and a single intraperitoneal (ip) injection of concentrated media conditioned by MSCs (CCM) or concentrated control media (CM). Controls received a sham injury and ip CM. Urethral and nerve function were assessed with leak point pressure (LPP) and pudendal nerve sensory branch potential (PNSBP) recordings 3 wk after injury. Urethral and pudendal nerve anatomy were assessed qualitatively by blinded investigators. Quantitative data were analyzed using one-way ANOVA and Holm-Sidak post hoc tests with P < 0.05 indicating significant differences. Both LPP and PNSBP were significantly decreased 3 wk after PNC + VD with saline or CM compared with sham-injured rats, but not with MSC or CCM. Elastic fiber density in the urethra increased and changed in orientation after PNC + VD, with a greater increase in elastic fibers with MSC or CCM. Pudendal nerve fascicles were less dense and irregularly shaped after PNC + VD and had reduced pathology with MSC or CCM. MSC and CCM provide similar protective effects after PNC + VD, suggesting that MSCs act via their secretions in this dual muscle and nerve injury.