Tissue Eng Regen Med.  2024 Jun;21(4):571-586. 10.1007/s13770-024-00629-1.

Exosomes Derived from Mouse Breast Carcinoma Cells Facilitate Diabetic Wound Healing

• Zhang C
• Xiao W
• Wang H
• Li L
• Yang Y
• Hao Y
• Xu Z
• Chen H
• Nan W

• KMID: 2556266
• DOI: http://doi.org/10.1007/s13770-024-00629-1

Abstract

BACKGROUND
Exosomes derived from breast cancer have been reported to play a role in promoting cell proliferation, migration, and angiogenesis, which has the potential to accelerate the healing process of diabetic wounds. The aim of this investigation was to examine the function of exosomes originating from 4T1 mouse breast carcinoma cells (TEXs) in the process of diabetic wound healing.
METHODS
The assessment of primary mouse skin fibroblasts cell proliferation and migration was conducted through the utilization of CCK-8 and wound healing assays, while the tube formation of HUVECs was evaluated by tube formation assay. High-throughput sequencing, RT-qPCR and cell experiments were used to detect the roles of miR-126a-3p in HUVECs functions in vitro. The in vivo study employed a model of full-thickness excisional wounds in diabetic subjects to explore the potential therapeutic benefits of TEXs. Immunohistochemical and immunofluorescent techniques were utilized to evaluate histological changes in skin tissues.
RESULTS
The findings suggested that TEXs facilitate diabetic wound healing through the activation of cell migration, proliferation, and angiogenesis. An upregulation of miR-126a-3p has been observed in TEXs, and it has demonstrated efficient transferability from 4T1 cells to HUVEC cells. The activation of the PI3K/Akt pathway has been attributed to miR-126a-3p derived from TEXs.
CONCLUSIONS
The promotion of chronic wound healing can be facilitated by TEXs through the activation of cellular migration, proliferation, and angiogenesis. The activation of the PI3K/Akt pathway by miR-126a-3p originating from TEXs has been discovered, indicating a potential avenue for enhancing the regenerative capabilities of wounds treated with TEXs.

Keyword

Exosomes; Cell proliferation and migration; Angiogenesis; miR-126a-3p; Wound healing