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

被引：49

作者：

Uchiyama, Akihiko ^{[1
]}

Motegi, Sei-ichiro ^{[1
]}

Sekiguchi, Akiko ^{[1
]}

Fujiwara, Chisako ^{[1
]}

Perera, Buddhini ^{[1
]}

Ogino, Sachiko ^{[1
]}

Yokoyama, Yoko ^{[1
]}

Ishikawa, Osamu ^{[1
]}

机构：

[1] Gunma Univ, Grad Sch Med, Dept Dermatol, 3-39-22 Showa, Maebashi, Gunma 3718511, Japan

来源：

JOURNAL OF DERMATOLOGICAL SCIENCE | 2017年 / 86卷 / 03期

关键词：

MFG-E8; Mesenchymal stem cells; Diabetic wound; Angiogenesis; Phagocytosis; ISCHEMIA-REPERFUSION INJURY; BONE-MARROW; MACROPHAGES; ANGIOGENESIS; GROWTH; POLARIZATION; MILK; SKIN; NEOVASCULARIZATION; TRANSPLANTATION;

D O I：

10.1016/j.jdermsci.2017.02.285

中图分类号：

R75 [皮肤病学与性病学];

学科分类号：

100206 ;

摘要：

Background: Diabetic wounds are intractable due to complex factors, such as the inhibition of angiogenesis, dysfunction of phagocytosis by macrophages and abnormal inflammatory responses. It is recognized that mesenchymal stem cells (MSCs) promote wound healing in diabetic mice. We previously demonstrated that MSCs produce large amounts of MFG-E8. Object: The objective was to ascertain the role of MSCs-derived MFG-E8 in murine diabetic wounds. Methods: MFG-E8 WT/KO MSCs or rMFG-E8 were subcutaneously injected around the wound in diabetic db/db mice, and wound areas were analyzed. Quantification of angiogenesis, infiltrating inflammatory cells, apoptotic cells at the wound area was performed by immunofluorescence staining and real-time PCR. Phagocytosis assay was performed using peritoneal macrophages from WT or db/db mice. Results: MFG-E8 expression in granulation tissue in diabetic mice was significantly reduced compared with that in non-diabetic mice. We next examined the effect of subcutaneous injection of MFG-E8 WT/KO MSCs around the wound. Diabetic wound healing was significantly accelerated by the injection of MSCs. Diabetic wound healing in MFG-E8 KO MSCs-injected wounds was significantly delayed compared to that in WT MSCs-injected wounds. The numbers of CD31(+) EC and NG2(+) pericytes, as well as M2 macrophages in wounds in KO MSCs-injected mice were significantly decreased. MFG-E8 WT MSCs treatment suppressed the number of apoptotic cells and TNF-alpha(+) cells in wounds. In an in vitro assay, MFG-E8 WT MSCs-conditioned medium enhanced phagocytosis of apoptotic cells by peritoneal macrophages from diabetic mice. Conclusion: MSCs-derived MFG-E8 might accelerate diabetic wound healing by promoting angiogenesis, the clearance of apoptotic cells, and the infiltration of M2 macrophages, and by suppressing inflammatory cytokines in wound area. (C) 2017 Japanese Society for Investigative Dermatology. Published by Elsevier Ireland Ltd. All rights reserved.

引用

页码：187 / 197

页数：11

共 49 条

[1] Systemic high-mobility group box 1 administration suppresses skin inflammation by inducing an accumulation of PDGFRα+ mesenchymal cells from bone marrow [J].