Mesenchymal stem cells-derived MFG-E8 accelerates diabetic cutaneous wound healing

Area of Science:

• Regenerative Medicine
• Wound Healing Research
• Diabetic Complications

Background:

• Diabetic wounds exhibit impaired healing due to inhibited angiogenesis, macrophage dysfunction, and inflammation.
• Mesenchymal stem cells (MSCs) are known to promote wound healing in diabetic models.
• MSCs were previously shown to produce significant amounts of MFG-E8.

Purpose of the Study:

• To investigate the specific role of MFG-E8, produced by MSCs, in the healing of murine diabetic wounds.
• To understand how MSCs-derived MFG-E8 influences key cellular processes in diabetic wound repair.

Main Methods:

• Subcutaneous injection of MFG-E8 wild-type (WT)/knockout (KO) MSCs or recombinant MFG-E8 into diabetic db/db mice wounds.
• Analysis of wound area, quantification of angiogenesis (CD31+ EC, NG2+ pericytes), inflammatory cells (TNF-α+), and apoptotic cells.
• In vitro phagocytosis assays using peritoneal macrophages from WT or diabetic mice.

Main Results:

• MFG-E8 expression was notably reduced in diabetic mouse wound granulation tissue.
• Diabetic wound healing was accelerated by MSC injection, with MFG-E8 KO MSCs showing delayed healing compared to WT MSCs.
• MFG-E8 WT MSCs treatment increased M2 macrophages, reduced apoptotic and TNF-α+ cells, and enhanced macrophage phagocytosis of apoptotic cells in vitro.

Conclusions:

• MSCs-derived MFG-E8 is a key factor in accelerating diabetic wound healing.
• MFG-E8 promotes angiogenesis, enhances apoptotic cell clearance, and modulates macrophage polarization towards the M2 phenotype.
• MFG-E8 may suppress inflammatory cytokines, contributing to improved diabetic wound repair.