Hydrogen Peroxide-Induced Senescence Reduces the Wound Healing-Promoting Effects of Mesenchymal Stem Cell-Derived Exosomes Partially via miR-146a

Evidence from laboratory and animal studies provides groundwork for understanding mechanisms and potential before human studies continue.

• Level A · Stronger Clinical Evidence
• Level B · Emerging clinical evidence with positive signals
• Level C · Early human research exploring benefits
• Level D · Scientific groundwork from lab and animal studies
• Emerging · Emerging topic under active research

Abstract (original English)

Mesenchymal stem cells (MSCs) have beneficial effects on wound healing. MSCs function through direct cell-cell communication or indirectly through paracrine secretion of exosomes. Here, we found that MSC-derived exosomes had pro-wound healing effects via promotion of angiogenesis; however, this promoting effect was significantly reduced when senescence was induced in parental MSCs by hydrogen peroxide (H 2 O 2 ). Further experiments showed that decreased miR-146a expression in exosomes derived from senescent MSCs (s-exo) contributed to these findings. In vitro , the pro-angiogenic effect of s-exo on tube formation in human umbilical vein endothelial cells was significantly reduced compared with that of exosomes derived from control MSCs (c-exo). In vivo , higher tube numbers and longer tube lengths were observed in the c-exo group compared with the s-exo group. Using microarray analysis, we found that miR-146a level in s-exo was lower than that in c-exo. Knockdown of miR-146a in c-exo decreased its capacity to promote angiogenesis, and overexpression of miR-146a in s-exo partially rescued its impaired pro-angiogenic capacity, thereby confirming that downregulation of miR-146a contributed to the reduced pro-wound healing capacity of s-exo. Our study is the first to demonstrate that cell senescence induced by H 2 O 2 alters the pro-angiogenic ability of exosomes by modulating the

Evidence level

Evidence from laboratory and animal studies provides groundwork for understanding mechanisms and potential before human studies continue.

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