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

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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.

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Funding

This research was funded Natural Science Foundation of Henan Province for Distinguished Young Scholars (202300410307) and the Key Scientific Research Projects of Institutions of Higher Learning in Henan Province (22A180009, 23A180019), and Key Scientific and Technological Research Project of Henan Province (222102310383, 222102310382, 232102311096).

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FC contributed to the conceptualization, writing-original draft, review and editing. LJ, PL, ZH and FY performed the experiments. YH, ZX and YL contributed to the validation and analysis. TR and XZ provided the technical support. JL gave funding support. All authors approved the final manuscript.

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Correspondence to Juntang Lin.

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This study was performed in line with the principles of the Declaration of Helsinki. This study was approved by the Ethics Committee of Xinxiang Medical University.

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Informed consent was obtained from all donors of MenSCs included in the study.

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The authors declare no competing interests.

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Cheng, F., Ji, L., Li, P. et al. Enhanced therapeutic potential of Flotillins-modified MenSCs by improve the survival, proliferation and migration. Mol Biol Rep 51, 680 (2024). https://doi.org/10.1007/s11033-024-09624-0

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