Departments of Obstetrics and Gynecology, National Clinical Research Center for Obstetric & Gynecologic Diseases, State Key Laboratory of Complex Severe and Rare Diseases, Peking Union Medical College Hospital, Chinese Academy of Medical Science and Peking Union Medical College, Beijing, China.
Department of Gynecology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan, China.
Cell Tissue Res. 2021 Dec;386(3):571-583. doi: 10.1007/s00441-021-03478-9. Epub 2021 Jul 15.
Vaginal structural defects are involved in pelvic organ prolapse (POP). We tested whether mesenchymal stem cell (MSC) therapy can repair the weakened vaginal wall of POP patients as a novel POP treatment. Ninety-six ovariectomized rats were divided into 4 groups (n = 24/group): saline (sal), collagen (col), sal + MSC, and col + MSC groups. Two weeks after ovariectomy, rats received subepithelial injection of 0.3 ml saline, 0.3 ml collagen I gel, and 0.3 ml saline: 3 × 10 human umbilical cord mesenchymal stem cells (HUMSCs), or 0.3 ml collagen I gel: 3 × 10 HUMSCs into the anterior vaginal wall. Eight additional rats underwent in vivo bioluminescence imaging (BLI) to evaluate in vivo cell viability. The BLI signal disappeared within 1 week after MSC injection, and no in vivo MSC differentiation was found. Collagen I content was significantly lower at 4 and 12 weeks in the two MSC groups than in the sal and col groups, while collagen III was significantly higher (P < 0.001). The fraction of smooth muscle in the nonvascular muscularis increased significantly in the two MSC groups at 12 weeks (P < 0.001). ACTA2 mRNA in the col + MSC group was significantly higher than that in the sal group at 2 and 4 weeks (P = 0.042 and P = 0.040). mRNA levels of angiogenic factors (bFGF or VEGF) in the two MSC groups were significantly higher than those in the sal and col groups at different time points. HUMSCs normalized the fibromuscular structures of the vaginal wall of ovariectomized rats potentially through a paracrine effect.
阴道结构缺陷与盆腔器官脱垂(POP)有关。我们测试了间充质干细胞(MSC)疗法是否可以修复 POP 患者的薄弱阴道壁,作为一种新的 POP 治疗方法。96 只去卵巢大鼠被分为 4 组(n = 24/组):盐水(sal)、胶原(col)、sal + MSC 和 col + MSC 组。去卵巢 2 周后,大鼠接受阴道上皮下注射 0.3 ml 盐水、0.3 ml 胶原 I 凝胶和 0.3 ml 盐水:3×10 个人脐带间充质干细胞(HUMSCs)或 0.3 ml 胶原 I 凝胶:3×10 HUMSCs 到阴道前壁。另外 8 只大鼠进行体内生物发光成像(BLI)以评估体内细胞活力。MSC 注射后 1 周内 BLI 信号消失,未发现体内 MSC 分化。在两个 MSC 组中,4 和 12 周时胶原 I 含量明显低于 sal 和 col 组,而胶原 III 含量明显升高(P < 0.001)。在两个 MSC 组中,非血管平滑肌的平滑肌部分在 12 周时显著增加(P < 0.001)。在 col + MSC 组中,ACTA2 mRNA 在 2 和 4 周时明显高于 sal 组(P = 0.042 和 P = 0.040)。在不同时间点,两个 MSC 组中血管生成因子(bFGF 或 VEGF)的 mRNA 水平明显高于 sal 和 col 组。HUMSCs 通过旁分泌作用使去卵巢大鼠的阴道壁纤维肌肉结构正常化。