Format

Send to

Choose Destination
Stem Cell Res Ther. 2016 Oct 28;7(1):158. doi: 10.1186/s13287-016-0403-3.

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.

Author information

1
Department of Pharmacology and Toxicology, University of Alabama at Birmingham School of Medicine, Birmingham, AL, 35294, USA.
2
Department of Physiology, Laboratory for Vascular Medicine and Stem Cell Biology, Medical Research Institute, School of Medicine, Pusan National University, Yangsan, 626-870, Republic of Korea.
3
Research Institute of Convergence Biomedical Science and Technology, Pusan National University School of Medicine, Yangsan, Republic of Korea.
4
Department of Immune Regulation, Research Centre for Hepatitis and Immunology, Research Institute, National Centre for Global Health and Medicine, Chiba, Japan.
5
Department of Regenerative Medicine Science, Tokai University School of Medicine, Kanagawa, Japan.
6
Division of Cardiology of Chonnam National University Hospital, Cardiovascular Convergence Research Center Nominated by Korea Ministry of Health and Welfare, Gwangju, 501-757, Republic of Korea. hyj200@hanmail.net.
7
Department of Physiology, Laboratory for Vascular Medicine and Stem Cell Biology, Medical Research Institute, School of Medicine, Pusan National University, Yangsan, 626-870, Republic of Korea. smkwon323@hotmail.com.

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.

KEYWORDS:

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

PMID:
27793180
PMCID:
PMC5084514
DOI:
10.1186/s13287-016-0403-3
[Indexed for MEDLINE]
Free PMC Article

Supplemental Content

Full text links

Icon for BioMed Central Icon for PubMed Central
Loading ...
Support Center