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Delivery of microRNA-423-5p by exosome from adipose-derived stem/stromal cells inhibits DVL3 to potentiate autologous fat graft survival through adipogenesis and inflammatory response

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Abstract

Autologous fat grafting represents a reconstructive technique but is limited by unstable graft retention. Based on existing reports and bioinformatics prediction, we hypothesized that delivering exosomes from human adipose-derived stem/stromal cells (hADSC-Exo) would increase fat graft survival and further explore the mechanism. hADSC-Exo were extracted and identified. An autologous fat grafting model was established using donor and recipient mice, followed by hADSC-Exo treatment. hADSC-Exo promoted the retention of autologous fat grafts in mice, along with increased adipocyte activity, angiogenesis, and decreased inflammation in grafts. Moreover, hADSC-Exo potentiated the adipose differentiation of 3T3-L1 cells, enhanced the angiogenic and migratory capacity of human umbilical vein endothelial cells, and inhibited the inflammation and viability of RAW 264.7 cells. The therapeutic effect of hADSC-Exo on fat grafting was associated with the delivery of microRNA (miR)-423-5p. Deletion of miR-423-5p in Exo impaired the function of hADSC-Exo on fat retention. miR-423-5p bound to DVL3 to suppress DVL3 expression, and DVL3 deletion promoted adipose differentiation of 3T3-L1 cells. In conclusion, our findings further widen the theoretical basis of the clinical application of hADSC-Exo in autologous fat grafts.

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Data availability

All other data supporting the findings of this study are available in the manuscript, as well as from the corresponding authors upon reasonable request.

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Acknowledgements

We thanks to the CAMS Innovation Fund for Medical Sciences (2021-I2M-1-052) for the funding support.

Funding

This study was supported by the CAMS Innovation Fund for Medical Sciences (2021-I2M-1–052).

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Authors and Affiliations

  1. Department of Adipose Remodeling, Plastic Surgery Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, No. 33, Badachu Road, Shijingshan District, 100144, Beijing, People’s Republic of China

    Jinglin Zhu, Xinyu Jia & Facheng Li

  2. Plastic Surgery Hospital, The Fourth Craniomaxillofacial Department, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, 100144, People’s Republic of China

    Fangning Zhao

  3. Department of Breast Surgery, The First Hospital of China Medical University, Shenyang, 110002, Liaoning, People’s Republic of China

    Yimeng Chai

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  1. Jinglin Zhu
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Contributions

Experiments were conceived and designed by JLZ; experiments were performed by FNZ and YMC; and data was analyzed by XYJ. The article was written by FCL. All authors read and approved the final manuscript.

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Correspondence to Facheng Li.

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The animal experimental protocol has been authorized by the ethics committee of the Chinese Academy of Medical Sciences and Peking Union Medical College and conformed to the Guide to the Care and Use of Experimental Animals.

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Zhu, J., Zhao, F., Chai, Y. et al. Delivery of microRNA-423-5p by exosome from adipose-derived stem/stromal cells inhibits DVL3 to potentiate autologous fat graft survival through adipogenesis and inflammatory response. Human Cell 37, 229–244 (2024). https://doi.org/10.1007/s13577-023-01010-5

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