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人脐带间充质干细胞重建去卵巢 Sprague-Dawley 大鼠的阴道壁:对盆底重建的启示。

Human umbilical cord mesenchymal stem cells reconstruct the vaginal wall of ovariectomized Sprague-Dawley rats: implications for pelvic floor reconstruction.

机构信息

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.

出版信息

Cell Tissue Res. 2021 Dec;386(3):571-583. doi: 10.1007/s00441-021-03478-9. Epub 2021 Jul 15.

DOI:10.1007/s00441-021-03478-9
PMID:34264376
Abstract

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.

摘要

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。

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本文引用的文献

1
Tissue Composition and Biomechanical Property Changes in the Vaginal Wall of Ovariectomized Young Rats.去卵巢年轻大鼠阴道壁组织成分和生物力学特性的变化。
Biomed Res Int. 2019 Jul 31;2019:8921284. doi: 10.1155/2019/8921284. eCollection 2019.
2
Human endometrial mesenchymal stem cells modulate the tissue response and mechanical behavior of polyamide mesh implants for pelvic organ prolapse repair.人子宫内膜间质干细胞调节聚酰胺网片植入物在盆腔器官脱垂修复中的组织反应和力学行为。
Tissue Eng Part A. 2014 Feb;20(3-4):785-98. doi: 10.1089/ten.TEA.2013.0170. Epub 2013 Nov 21.
脐带间充质基质细胞来源的外泌体促进盆腔器官脱垂患者成纤维细胞的胶原蛋白生成。
World J Stem Cells. 2024 Jun 26;16(6):708-727. doi: 10.4252/wjsc.v16.i6.708.
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Preliminary study on mesenchymal stem cells in repairing nerve injury in pelvic floor denervation.间充质干细胞修复盆底去神经支配后神经损伤的初步研究
Front Bioeng Biotechnol. 2023 Jun 22;11:1190068. doi: 10.3389/fbioe.2023.1190068. eCollection 2023.
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Exosomes derived from mesenchymal stromal cells: a promising treatment for pelvic floor dysfunction.间充质基质细胞衍生的外泌体:盆底功能障碍治疗的新希望。
Hum Cell. 2023 May;36(3):937-949. doi: 10.1007/s13577-023-00887-6. Epub 2023 Mar 20.
6
Human Umbilical Cord-Based Therapeutics: Stem Cells and Blood Derivatives for Female Reproductive Medicine.基于人脐带的治疗方法:用于女性生殖医学的干细胞和血液衍生物。
Int J Mol Sci. 2022 Dec 14;23(24):15942. doi: 10.3390/ijms232415942.