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激活 BMP7-Smad5 信号通路促进小鼠自体脂肪来源干细胞与 ShakeGel™3D 复合物局部注射修复宫腔粘连

Repair abilities of mouse autologous adipose-derived stem cells and ShakeGel™3D complex local injection with intrauterine adhesion by BMP7-Smad5 signaling pathway activation.

机构信息

Department of Gynaecology and Obstetrics, The Second Affiliated Hospital of Fujian Medical University, No.34 North Zhongshan Road, Quanzhou, 362000, Fujian Province, China.

Department of Anaesthesiology, the Second Affiliated Hospital, Fujian Medical University, Quanzhou, China.

出版信息

Stem Cell Res Ther. 2021 Mar 18;12(1):191. doi: 10.1186/s13287-021-02258-0.

Abstract

BACKGROUND

The objective was to explore the therapeutic effect of autologous adipose-derived stem cells (ADSCs) combined with ShakeGel™3D transplantation to activate the BMP7-Smad5 signaling pathway to treat intrauterine adhesions (IUA).

METHODS

Autologous ADSCs were isolated and then merged with ShakeGel™3D. The IUA model was established by mechanical injury. The third generation of autologous ADSCs was injected directly into the uterus in combination with ShakeGel™3D. After 7 days of treatment, endometrial morphology, number of endometrial glands, endometrial fibrosis area, and fibrosis biomarker analysis by RT-PCR and IHC were examined. BMP7 and phosphorylation of Smad5 were also detected, and the recovery of infertility function in treated mice was evaluated.

RESULTS

Fluorescence-activated cell sorting (FACS) showed that autologous ADSCs expressed CD105 (99.1%), CD29 (99.6%), and CD73 (98.9%). Autologous ADSCs could still maintain a good growth state in ShakeGel™3D. Histological examination revealed that the number of endometrial glands increased significantly, and the area of fibrosis decreased. At the same time, the expression of BMP7 and Smad5 in the ADSCs + Gel group was significantly upregulated, and the final reproductive function of this group was partly recovered.

CONCLUSIONS

Autologous ADSCs can be used in combination with ShakeGel™3D to maintain functionality and create a viable three-dimensional growth environment. The combined transplantation of autologous ADSCs and ShakeGel™3D promotes the recovery of damaged endometrial tissue by increasing BMP7-Smad5 signal transduction, resulting in endometrium thickening, increased number of glands, and decreased fibrosis, leading to restoration of partial fertility.

摘要

背景

本研究旨在探索自体脂肪来源干细胞(ADSCs)联合 ShakeGel™3D 移植激活 BMP7-Smad5 信号通路治疗宫腔粘连(IUA)的疗效。

方法

分离自体 ADSCs 并与 ShakeGel™3D 融合。通过机械损伤建立 IUA 模型,将第三代自体 ADSCs 直接注入子宫,结合 ShakeGel™3D 移植。治疗 7 天后,通过 RT-PCR 和 IHC 检测子宫内膜形态、子宫内膜腺体数量、子宫内膜纤维化面积和纤维化生物标志物分析,检测 BMP7 和 Smad5 磷酸化水平,并评估治疗后小鼠生育功能的恢复情况。

结果

流式细胞术(FACS)显示,自体 ADSCs 表达 CD105(99.1%)、CD29(99.6%)和 CD73(98.9%)。自体 ADSCs 在 ShakeGel™3D 中仍能保持良好的生长状态。组织学检查显示,子宫内膜腺体数量明显增加,纤维化面积减少。同时,ADSCs+Gel 组中 BMP7 和 Smad5 的表达明显上调,该组的最终生殖功能部分恢复。

结论

自体 ADSCs 可与 ShakeGel™3D 联合使用,以维持其功能并创造可行的三维生长环境。自体 ADSCs 联合 ShakeGel™3D 移植通过增加 BMP7-Smad5 信号转导促进受损子宫内膜组织的恢复,导致子宫内膜增厚、腺体数量增加、纤维化减少,从而部分恢复生育能力。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a264/7977602/08036fa6df86/13287_2021_2258_Fig1_HTML.jpg

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