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通过提高存活率、增殖率和迁移率来增强 Flotillins 修饰的 MenSCs 的治疗潜力。

Enhanced therapeutic potential of Flotillins-modified MenSCs by improve the survival, proliferation and migration.

机构信息

Stem Cell and Biotherapy Engineering Research Center of Henan, College of Life Science and Technology, Xinxiang Medical University, Xinxiang, 453003, China.

Henan Joint International Research Laboratory of Stem Cell Medicine, School of Medical Engineering, Xinxiang Medical University, Xinxiang, 453003, China.

出版信息

Mol Biol Rep. 2024 May 25;51(1):680. doi: 10.1007/s11033-024-09624-0.

Abstract

Menstrual blood-derived endometrial stem cells (MenSCs) have attracted increasing interest due to their excellent safety, and lack of ethical dilemma as well as their ability to be periodically obtained in a noninvasive manner. However, although preclinical research as shown the therapeutic potential of MenSCs in several diseases, their poor cell survival and low engraftment at disease sites reduce their clinical efficacy. Flotillins (including Flot1 and Flot2) are implicated in various cellular processes, such as vesicular trafficking, signal transduction, cell proliferation, migration and apoptosis. In this study, we aimed to determine the effects of Flotillins on MenSCs survival, proliferation and migration. Our experimental results show that MenSCs were modified to overexpress Flot1 and/or Flot2 without altering their intrinsic characteristics. Flot1 and Flot2 co-overexpression promoted MenSC viability and proliferation capacity. Moreover, Flot1 or Flot2 overexpression significantly promoted the migration and inhibited the apoptosis of MenSCs compared with the negative control group, and these effects were stronger in the Flot1 and Flot2 gene co-overexpression group. However, these effects were significantly reversed after Flot1 and/or Flot2 knockdown. In conclusion, our results indicate that Flot1 and Flot2 overexpression in MenSCs improved their proliferation and migration and inhibited their apoptosis, and this might be an effective approach to improve the efficiency of cell-based therapies.

摘要

经血来源的子宫内膜干细胞(MenSCs)由于其良好的安全性、不存在伦理问题以及能够以非侵入性的方式定期获取而引起了越来越多的关注。然而,尽管临床前研究表明 MenSCs 在多种疾病中有治疗潜力,但它们在疾病部位的细胞存活率低和植入率低降低了它们的临床疗效。Flotillins(包括 Flot1 和 Flot2)参与多种细胞过程,如囊泡运输、信号转导、细胞增殖、迁移和凋亡。在这项研究中,我们旨在确定 Flotillins 对 MenSCs 存活、增殖和迁移的影响。我们的实验结果表明,MenSCs 被修饰为过表达 Flot1 和/或 Flot2,而不改变其内在特性。Flot1 和 Flot2 的共过表达促进了 MenSC 的活力和增殖能力。此外,与阴性对照组相比,Flot1 或 Flot2 的过表达显著促进了 MenSCs 的迁移并抑制了其凋亡,而在 Flot1 和 Flot2 基因共过表达组中这些效果更强。然而,Flot1 和/或 Flot2 敲低后,这些效果明显逆转。总之,我们的结果表明,MenSCs 中 Flot1 和 Flot2 的过表达提高了它们的增殖和迁移能力,并抑制了它们的凋亡,这可能是提高基于细胞的治疗效率的有效方法。

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