4.5 Article

Exosomes from adipose-derived mesenchymal stem cells promote survival of fat grafts by regulating macrophage polarization via let-7c

Journal

ACTA BIOCHIMICA ET BIOPHYSICA SINICA
Volume 53, Issue 4, Pages 501-510

Publisher

SCIENCE PRESS
DOI: 10.1093/abbs/gmab018

Keywords

adipose-derived mesenchymal stem cells; exosome; fat graft; macrophages; let-7c; C/EBP-delta

Funding

  1. Fundamental Research Funds for the Central Universities in Xi'an Jiaotong University [xjj2018116]

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The study demonstrates that exosomes derived from AD-MSCs promote the survival of fat grafts by regulating macrophage polarization through let-7c, shedding light on the immunotherapeutic potential of AD-MSC-derived exosomes in fat grafting.
The rate of fat graft survival is a critical aspect of successful surgery and has been a matter of concern for over 20 years. Owing to their anti-inflammatory effects and regenerative property, adipose-derived mesenchymal stem cells (AD-MSCs) have been adapted for clinical application in fat grafting, although the mechanism underlying their action remains unclear. Recently, exosomes derived from MSCs were suggested as a better alternative, and these exosomes have also been applied in diverse clinical therapies. Accumulating evidence suggests that MSCs modulate macrophage differentiation via exosome secretion, and the connection between macrophage regulation and the rate of fat graft survival has been established. Here, we identified that let-7c, the key factor in the regulatory process, is shuttled by AD-MSC-derived exosomes to downregulate the transcription factor CCAAT/enhancer-binding protein (C/EBP)-delta. The downregulation of C/EBP-delta resulted in the attenuation of pro-inflammatory M1 macrophages and elevation of anti-inflammatory M2 macrophages. These results suggest that AD-MSC-derived exosomes promote the survival of fat grafts by regulating macrophage polarization via let-7c. This is the first study to elucidate the mechanism underlying the promotion of the fat graft survival rate by AD-MSCs and to evaluate the immunotherapeutic potential of AD-MSC-derived exosomes in fat grafting.

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