Division Woman and Baby, University Medical Center Utrecht, Heidelberglaan 100, 3584CX, Utrecht, the Netherlands.
Advanced Platform Technology Center, Louis Stokes Cleveland VA Medical Center, Cleveland, OH, USA.
Int Urogynecol J. 2023 Jul;34(7):1635-1644. doi: 10.1007/s00192-022-05439-4. Epub 2023 Jan 20.
New treatments are needed for pelvic floor disorders. ReGeneraTing Agent® (RGTA®) is a promising regenerative therapy. Therefore, the objective of this study was to compare regenerative abilities of mesenchymal stem cells (MSCs) and RGTA® on regeneration after simulated childbirth injury in rats.
Rats underwent pudendal nerve crush and vaginal distension (PNC+VD) or sham injury. Rats that underwent PNC+VD were treated intravenously with vehicle, MSCs or RGTA® 1 h, 7 days, and 14 days after surgery. Sham rats received 1 ml vehicle at all time points. After 21 days, urethral function and pudendal nerve function were tested. Vaginal tissues were harvested for biomechanical testing and histology. Biaxial testing was performed to measure tissue stiffness.
PNC+VD decreased urethral and pudendal nerve function compared with sham. Vaginal wall stiffness was significantly decreased in longitudinal and transverse tissue axes after PNC+VD compared with sham. MSC or RGTA® did not restore urethral or pudendal nerve function. However, MSC treatment resolved loss in vaginal wall stiffness in both tissue axes and improved collagen content within the vaginal wall. RGTA® treatment increased vaginal wall anisotropy by increasing relative stiffness in the longitudinal direction. PNC+VD (with vehicle or MSCs) enhanced elastogenesis, which was not observed after RGTA® treatment.
Treatment with MSCs facilitated recovery of vaginal wall biomechanical properties and connective tissue composition after PNC+VD, whereas treatment with RGTA® resulted in anisotropic biomechanical changes. This indicates that MSCs and RGTA® promote different aspects of vaginal tissue regeneration after simulated childbirth injury.
需要新的治疗方法来治疗盆底功能障碍。再生剂（RGTA）是一种很有前途的再生疗法。因此，本研究的目的是比较间充质干细胞（MSCs）和 RGTA 在大鼠模拟分娩损伤后的再生能力。
大鼠行阴部神经挤压和阴道扩张（PNC+VD）或假损伤。PNC+VD 大鼠在手术后 1 小时、7 天和 14 天分别静脉注射载体、MSCs 或 RGTA。假损伤大鼠在所有时间点均给予 1ml 载体。21 天后，测试尿道功能和阴部神经功能。采集阴道组织进行生物力学测试和组织学检查。双轴测试用于测量组织硬度。
与假损伤相比，PNC+VD 降低了尿道和阴部神经功能。与假损伤相比，PNC+VD 后阴道壁的纵向和横向组织轴的硬度显著降低。MSCs 或 RGTA 均不能恢复尿道或阴部神经功能。然而，MSC 治疗可恢复阴道壁硬度在两个组织轴上的丧失，并改善阴道壁内的胶原含量。RGTA 治疗通过增加纵向方向的相对硬度增加了阴道壁各向异性。PNC+VD（用载体或 MSCs）增强了弹性生成，而 RGTA 治疗后则没有观察到这种情况。
与 PNC+VD 后使用载体或 MSCs 治疗一样，MSCs 治疗促进了阴道壁生物力学特性和结缔组织组成的恢复，而 RGTA 治疗导致了各向异性的生物力学变化。这表明 MSCs 和 RGTA 在模拟分娩损伤后促进了阴道组织再生的不同方面。
