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热敏水凝胶联合牙髓干细胞在动物模型中对损伤输卵管黏膜的应用。

Application of thermosensitive-hydrogel combined with dental pulp stem cells on the injured fallopian tube mucosa in an animal model.

作者信息

Luo Lihua, Zhu Qunyan, Li Yejian, Hu Fengting, Yu Jiangtao, Liao Xiangyan, Xing Zhenjie, He Yan, Ye Qingsong

机构信息

School and Hospital of Stomatology, Wenzhou Medical University, Wenzhou, Zhejiang, China.

The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, Zhejiang, China.

出版信息

Front Bioeng Biotechnol. 2023 Jan 6;10:1062646. doi: 10.3389/fbioe.2022.1062646. eCollection 2022.

DOI:10.3389/fbioe.2022.1062646
PMID:36686246
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC9852820/
Abstract

Fallopian tube (FT) injury is an important factor that can lead to tubal infertility. Stem-cell-based therapy shows great potential for the treatment of injured fallopian tube. However, little research has shown that mesenchymal stem cells (MSCs) can be used to treat fallopian tube damage by injection. In this study, we transplanted PF127 hydrogel encapsulating dental pulp stem cells (DPSCs) into the injured sites to promote the repair and regeneration of fallopian tube injury. The properties of dental pulp stem cells were evaluated by flow cytometry, immunofluorescence analysis, and multi-differentiation detection. The immunomodulatory and angiogenic characteristics of dental pulp stem cells were analyzed on the basis of the detection of inflammatory factor expression and the formation of capillary-like structures, respectively. The biocompatibility of PF127 hydrogel was evaluated by using Live/Dead and CCK-8 assays. The effects of PF127 hydrogel containing dental pulp stem cells on the repair and regeneration of fallopian tube injury were evaluated by histological analysis [e.g., hematoxylin and eosin (H&E) and Masson's trichrome staining, TUNEL staining, immunofluorescence staining, and immunohistochemistry], Enzyme-linked immunosorbent assay (ELISA), and RT-PCR detections. Dental pulp stem cells had MSC-like characteristics and great immunomodulatory and angiogenic properties. PF127 hydrogel had a thermosensitive feature and great cytocompatibility with dental pulp stem cells. In addition, our results indicated that PF127 hydrogel containing dental pulp stem cells could promote the repair and regeneration of fallopian tube damage by inhibiting cell apoptosis, stimulating the secretion of angiogenic factors, promoting cell proliferation, modulating the secretion of inflammatory factors, and restoring the secretion of epithelial cells. In this study, our results reported that injection of PF127 hydrogel encapsulating dental pulp stem cells into the injured sites could provide an attractive strategy for the future treatment of fallopian tube injury in clinical settings.

摘要

输卵管（FT）损伤是导致输卵管性不孕的一个重要因素。基于干细胞的疗法在治疗受损输卵管方面显示出巨大潜力。然而，很少有研究表明间充质干细胞（MSCs）可通过注射用于治疗输卵管损伤。在本研究中，我们将包裹牙髓干细胞（DPSCs）的PF127水凝胶移植到损伤部位，以促进输卵管损伤的修复和再生。通过流式细胞术、免疫荧光分析和多向分化检测对牙髓干细胞的特性进行评估。分别基于炎症因子表达检测和毛细血管样结构形成，分析牙髓干细胞的免疫调节和血管生成特性。通过活/死细胞检测和CCK-8检测评估PF127水凝胶的生物相容性。通过组织学分析[如苏木精和伊红（H&E）染色、Masson三色染色、TUNEL染色、免疫荧光染色和免疫组织化学]、酶联免疫吸附测定（ELISA）和RT-PCR检测，评估含牙髓干细胞的PF127水凝胶对输卵管损伤修复和再生的影响。牙髓干细胞具有间充质干细胞样特性以及强大的免疫调节和血管生成特性。PF127水凝胶具有热敏特性，与牙髓干细胞具有良好的细胞相容性。此外，我们的结果表明，含牙髓干细胞的PF127水凝胶可通过抑制细胞凋亡、刺激血管生成因子分泌、促进细胞增殖、调节炎症因子分泌以及恢复上皮细胞分泌，来促进输卵管损伤的修复和再生。在本研究中，我们的结果表明，将包裹牙髓干细胞的PF127水凝胶注射到损伤部位可为未来临床治疗输卵管损伤提供一种有吸引力的策略。

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