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UC-MSCs 通过激活体外卵巢培养系统中的 Wnt/β-catenin 通路促进冻融卵巢血管生成。

UC-MSCs promote frozen-thawed ovaries angiogenesis via activation of the Wnt/β-catenin pathway in vitro ovarian culture system.

机构信息

Reproductive Medicine Center, Department of Obstetrics and Gynecology, The First Affiliated Hospital of Anhui Medical University, No 218 Jixi Road, Hefei, 230022, Anhui, China.

Anhui Province Key Laboratory of Reproductive Health and Genetics, Anhui Medical University, No 81 Meishan Road, Hefei, 230032, Anhui, China.

出版信息

Stem Cell Res Ther. 2022 Jul 15;13(1):296. doi: 10.1186/s13287-022-02989-8.

DOI:10.1186/s13287-022-02989-8
PMID:35841074
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC9284710/
Abstract

BACKGROUND

Ovarian tissue cryopreservation and transplantation are novel therapeutic approaches for fertility preservation. However, follicle loss caused by ischemic and hypoxic damage is one of the issues after frozen-thawed ovarian tissue transplantation. Promoting angiogenesis in grafts is the key to restore cryopreserved ovarian function. Mesenchymal stem cells (MSCs) have been reported to facilitate angiogenesis in the cryopreserved ovarian tissue transplantation. However, the risk of embolization, immunogenic effect and tumorigenesis hinders the clinical application of MSCs to human organ transplantation. In this study, we established an in vitro ovarian culture system to restore frozen-thawed ovarian function before transplantation with the application of umbilical cord mesenchymal stem cells (UC-MSCs), and explored the effects of UC-MSCs on frozen-thawed ovaries in vitro ovarian culture system and the mechanisms of UC-MSCs on the angiogenesis of frozen-thawed ovaries.

METHODS

A simple in vitro three dimensional (3D) ovarian culture system using Matrigel was established to support to an ideal niche, and ovary was alone cultured in the 24-well plate as a control. We also evaluated the effects of UC-MSCs treatment on ovarian function with or without Matrigel support. All thawed ovaries were randomly divided into control group (Matrigel-/UC-MSCs-), Matrigel group (Matrigel+/UC-MSCs-), UC-MSCs group (Matrigel-/UC-MSCs+) and UC-MSCs + Matrigel group (Matrigel+/UC-MSCs+). HE staining was used to detect the histological structure of follicles and TUNEL staining was used to detect cell apoptosis. The number of microvessels was counted to evaluate neovascularization. The mRNA expression of VEGFA, IGF1 and ANGPT2 were detected by RT-PCR. Western blotting was used to measure the expression of GSK-3β, β-catenin and p-β-catenin.

RESULTS

In the absence of UC-MSCs, 3D culture system supported by Matrigel showed significantly improved follicular development and microvascular number. Additionally, UC-MSCs were also found to effectively improve follicular development and microvascular number regardless of the culture condition used. However, alleviated follicular apoptosis, increased mRNA expression of angiogenesis-related gene and activated Wnt/β-catenin pathway occurred only in the UC-MSCs + Matrigel group. Besides, with the application of IWP-2 in UC-MSCs + Matrigel group, Wnt//β-catenin pathway could be blocked by IWP-2 serving as one of Wnt/β-catenin pathway inhibitors.

CONCLUSIONS

This in vitro study showed the beneficial effects of UC-MSCs on thawed ovaries and explored a potential mechanism inducing angiogenesis. In particular, 3D ovarian culture system supported by Matrigel further improved UC-MSCs treatment. The in vitro culture system using Matrigel and UC-MSCs may provide a potential treatment strategy for improving the success rate of thawed ovaries transplantation.

摘要

背景

卵巢组织冻存和移植是保留生育力的新的治疗方法。然而，冷冻解冻卵巢组织移植后，由缺血缺氧损伤引起的卵泡丢失是问题之一。促进移植物中的血管生成是恢复冷冻卵巢功能的关键。间充质干细胞（MSCs）已被报道可促进冷冻卵巢组织移植中的血管生成。然而，栓塞、免疫原性和致瘤的风险阻碍了间充质干细胞在人体器官移植中的临床应用。在这项研究中，我们建立了一种体外卵巢培养系统，在移植前应用脐带间充质干细胞（UC-MSCs）来恢复冷冻解冻的卵巢功能，并探讨了 UC-MSCs 对体外卵巢培养系统中冷冻解冻卵巢的作用以及 UC-MSCs 对冷冻解冻卵巢血管生成的作用机制。

方法

建立了一个简单的体外三维（3D）卵巢培养系统，使用 Matrigel 来支持理想的巢位，并将卵巢单独培养在 24 孔板中作为对照。我们还评估了 UC-MSCs 治疗对有或没有 Matrigel 支持的卵巢功能的影响。所有解冻的卵巢均随机分为对照组（Matrigel-/UC-MSCs-）、Matrigel 组（Matrigel+/UC-MSCs-）、UC-MSCs 组（Matrigel-/UC-MSCs+）和 UC-MSCs+Matrigel 组（Matrigel+/UC-MSCs+）。HE 染色用于检测卵泡的组织学结构，TUNEL 染色用于检测细胞凋亡。计数微血管数量以评估新血管生成。通过 RT-PCR 检测 VEGFA、IGF1 和 ANGPT2 的 mRNA 表达。Western blot 用于测量 GSK-3β、β-catenin 和 p-β-catenin 的表达。

结果

在没有 UC-MSCs 的情况下，Matrigel 支持的 3D 培养系统显示出明显改善的卵泡发育和微血管数量。此外，无论使用何种培养条件，UC-MSCs 也被发现可有效改善卵泡发育和微血管数量。然而，只有在 UC-MSCs+Matrigel 组中，才观察到卵泡凋亡减少、血管生成相关基因的 mRNA 表达增加和 Wnt/β-catenin 通路激活。此外，在用 Wnt/β-catenin 通路抑制剂 IWP-2 处理 UC-MSCs+Matrigel 组后，Wnt/β-catenin 通路可被 IWP-2 阻断。

结论

这项体外研究表明 UC-MSCs 对解冻卵巢有有益的影响，并探讨了诱导血管生成的潜在机制。特别是，Matrigel 支持的 3D 卵巢培养系统进一步提高了 UC-MSCs 的治疗效果。使用 Matrigel 和 UC-MSCs 的体外培养系统可能为提高解冻卵巢移植成功率提供一种潜在的治疗策略。

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本文引用的文献

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Biopreserv Biobank. 2022 Apr;20(2):168-175. doi: 10.1089/bio.2021.0048. Epub 2021 Nov 16.
2
Vascular remodeling by placenta-derived mesenchymal stem cells restores ovarian function in ovariectomized rat model via the VEGF pathway.胎盘来源间充质干细胞通过 VEGF 通路的血管重塑作用恢复卵巢切除大鼠模型的卵巢功能。
Lab Invest. 2021 Mar;101(3):304-317. doi: 10.1038/s41374-020-00513-1. Epub 2020 Dec 10.
3
Exosomes Derived from Umbilical Cord Mesenchymal Stem Cells Alleviate Mifepristone-Induced Human Endometrial Stromal Cell Injury.
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Reprod Biol Endocrinol. 2024 Nov 7;22(1):137. doi: 10.1186/s12958-024-01310-x.
4
Enhancement of Vascularization and Ovarian Follicle Survival Using Stem Cells in Cryopreserved Ovarian Tissue Transplantation-A Systematic Review.在冷冻保存的卵巢组织移植中使用干细胞增强血管生成和卵泡存活——一项系统综述
Biology (Basel). 2024 May 14;13(5):342. doi: 10.3390/biology13050342.
5
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Cancers (Basel). 2023 Dec 26;16(1):125. doi: 10.3390/cancers16010125.
6
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6
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7
Immunomodulation by Mesenchymal Stem Cells (MSCs): Mechanisms of Action of Living, Apoptotic, and Dead MSCs.间充质干细胞（MSCs）的免疫调节作用：活细胞、凋亡细胞和死亡细胞 MSC 的作用机制。
Front Immunol. 2019 Jun 4;10:1191. doi: 10.3389/fimmu.2019.01191. eCollection 2019.
8
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In Vitro Cell Dev Biol Anim. 2019 Apr;55(4):302-311. doi: 10.1007/s11626-019-00337-4. Epub 2019 Feb 28.
9
Human amnion-derived mesenchymal stem cell (hAD-MSC) transplantation improves ovarian function in rats with premature ovarian insufficiency (POI) at least partly through a paracrine mechanism.人羊膜间充质干细胞（hAD-MSC）移植通过旁分泌机制至少部分改善了卵巢早衰（POI）大鼠的卵巢功能。
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10
3D organ models-Revolution in pharmacological research?3D 器官模型——药理学研究的革命？
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