Exosomes from adipose-derived stem cells regulate macrophage polarization and accelerate diabetic wound healing via the circ-Rps5/miR-124-3p axis.

Publisher: John Wiley and Sons Ltd Country of Publication: England NLM ID: 101635460 Publication Model: Print Cited Medium: Internet ISSN: 2050-4527 (Electronic) Linking ISSN: 20504527 NLM ISO Abbreviation: Immun Inflamm Dis Subsets: MEDLINE

Original Publication: [Oxford] : John Wiley and Sons Ltd, [2013]-

Exosomes*/metabolism ; Macrophages*/metabolism ; Macrophages*/immunology ; MicroRNAs*/genetics ; Wound Healing*; Animals ; Male ; Mice ; Adipose Tissue/cytology ; Adipose Tissue/metabolism ; Autophagy ; Diabetes Mellitus, Experimental/therapy ; Macrophage Activation/immunology ; Mice, Inbred C57BL ; RAW 264.7 Cells ; RNA, Circular/genetics ; Stem Cells/metabolism

Background: Adipose-derived stem cells (ADSCs) hold promising application prospects in the treatment of diabetic wounds, although the underlying mechanisms of repair have not been fully elucidated. This research aimed to elucidate the mechanisms by which ADSCs promote wound healing.
Methods: Exosomes from ADSCs were isolated and circRps5 level was identified. To investigate the role of circRps5 in the regulation, exosomes from differently treated ADSCs were used. Different exosomes were injected into the edge of the wound in diabetic mice, and the effects on wound healing status, pathology, collagen, cytokines, and macrophage phenotype were assessed. Raw264.7 cells were co-treated with high glucose and exosomes, and then cell phenotype and autophagy were examined in vitro, followed by the evaluation of miR-124-3p's impact on cell phenotype.
Results: Exosomes from ADSCs were isolated and identified using nanoparticle tracking analysis and exosome markers. Overexpression of circRps5 accelerated wound healing, reduced inflammatory response, enhanced collagen production, and promoted the M2 transformation of macrophages. In high glucose-induced macrophages, its overexpression also inhibited excessive autophagy. When macrophages overexpressed miR-124-3p, the induction of the M2 phenotype was suppressed. Luciferase reporter assay proved the combination of circRps5 and miR-124-3p.
Conclusion: This study identifies that circRps5 carried by ADSC-Exos promotes macrophage M2 polarization through miR-124-3p. These findings provide valuable insights into the mechanism of ADSC-Exos for treating refractory diabetic wounds, laying a solid theoretical groundwork for future clinical development.
(© 2024 The Authors. Immunity, Inflammation and Disease published by John Wiley & Sons Ltd.)

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Keywords: ADSCs; diabetes; exosomes; macrophage polarization; wound healing

0 (MicroRNAs)
0 (Mirn124 microRNA, mouse)
0 (RNA, Circular)

Date Created: 20240618 Date Completed: 20240618 Latest Revision: 20240628

20240628

PMC11184652

10.1002/iid3.1274

38888351