Specific disruption of Lnk in murine endothelial progenitor cells promotes dermal wound healing via enhanced vasculogenesis, activation of myofibroblasts, and suppression of inflammatory cell recruitment

Stem Cell Research & Therapy

Satoshi Takaki¹  Jun Hee Lee²  Seung Taek Ji³  Sang-Mo Kwon³  Takayuki Asahara⁴  Young-Joon Hong⁵  Jaeho Kim⁶ 

[1] Department of Immune Regulation, Research Centre for Hepatitis and Immunology, Research Institute, National Centre for Global Health and Medicine;Department of Pharmacology and Toxicology, University of Alabama at Birmingham School of Medicine;Department of Physiology, Laboratory for Vascular Medicine and Stem Cell Biology, Medical Research Institute, School of Medicine, Pusan National University;Department of Regenerative Medicine Science, Tokai University School of Medicine;Division of Cardiology of Chonnam National University Hospital, Cardiovascular Convergence Research Center Nominated by Korea Ministry of Health and Welfare;Research Institute of Convergence Biomedical Science and Technology, Pusan National University School of Medicine;

关键词: Endothelial progenitor cell;    Wound healing;    Neovascularization;    Anti-inflammatory;    Cell-based therapy;   

DOI  :  10.1186/s13287-016-0403-3

来源: DOAJ

【 摘 要 】

Abstract Background Although endothelial progenitor cells (EPCs) contribute to wound repair by promoting neovascularization, the mechanism of EPC-mediated wound healing remains poorly understood due to the lack of pivotal molecular targets of dermal wound repair. Methods and Results We found that genetic targeting of the Lnk gene in EPCs dramatically enhances the vasculogenic potential including cell proliferation, migration, and tubule-like formation as well as accelerates in vivo wound healing, with a reduction in fibrotic tissue and improved neovascularization via significant suppression of inflammatory cell recruitment. When injected into wound sites, Lnk -/- EPCs gave rise to a significant number of new vessels, with remarkably increased survival of transplanted cells and decreased recruitment of cytotoxic T cells, macrophages, and neutrophils, but caused activation of fibroblasts in the wound-remodeling phase. Notably, in a mouse model of type I diabetes, transplanted Lnk -/- EPCs induced significantly better wound healing than Lnk +/+ EPCs did. Conclusions The specific targeting of Lnk may be a promising EPC-based therapeutic strategy for dermal wound healing via improvement of neovascularization but inhibition of excessive inflammation as well as activation of myofibroblasts during dermal tissue remodeling.

【 授权许可】

Unknown