VEGF165 induces differentiation of hair follicle stem cells into endothelial cells and plays a role in in vivo angiogenesis

J Cell Mol Med. 2017 Aug;21(8):1593-1604. doi: 10.1111/jcmm.13089. Epub 2017 Feb 28.

Abstract

Within the vascular endothelial growth factor (VEGF) family of five subtypes, VEGF165 secreted by endothelial cells has been identified to be the most active and widely distributed factor that plays a vital role in courses of angiogenesis, vascularization and mesenchymal cell differentiation. Hair follicle stem cells (HFSCs) can be harvested from the bulge region of the outer root sheath of the hair follicle and are adult stem cells that have multi-directional differentiation potential. Although the research on differentiation of stem cells (such as fat stem cells and bone marrow mesenchymal stem cells) to the endothelial cells has been extensive, but the various mechanisms and functional forms are unclear. In particular, study on HFSCs' directional differentiation into vascular endothelial cells using VEGF165 has not been reported. In this study, VEGF165 was used as induction factor to induce the differentiation from HFSCs into vascular endothelial cells, and the results showed that Notch signalling pathway might affect the differentiation efficiency of vascular endothelial cells. In addition, the in vivo transplantation experiment provided that HFSCs could promote angiogenesis, and the main function is to accelerate host-derived neovascularization. Therefore, HFSCs could be considered as an ideal cell source for vascular tissue engineering and cell transplantation in the treatment of ischaemic diseases.

Keywords: VEGF165; hair follicle stem cells; inducible factor; tissue engineering; vascular endothelial cells.

MeSH terms

  • Animals
  • Antigens, CD / genetics
  • Antigens, CD / metabolism
  • Cadherins / genetics
  • Cadherins / metabolism
  • Cell Differentiation
  • Collagen / chemistry
  • Drug Combinations
  • Endothelial Cells / cytology
  • Endothelial Cells / drug effects*
  • Endothelial Cells / metabolism
  • Female
  • Gene Expression Regulation
  • Hair Follicle / cytology
  • Hair Follicle / drug effects*
  • Hair Follicle / metabolism
  • Hindlimb / blood supply
  • Hindlimb / drug effects
  • Humans
  • Ischemia / genetics
  • Ischemia / metabolism
  • Ischemia / pathology
  • Ischemia / therapy*
  • Laminin / chemistry
  • Male
  • Mice
  • Mice, Nude
  • Neovascularization, Physiologic / drug effects*
  • Platelet Endothelial Cell Adhesion Molecule-1 / genetics
  • Platelet Endothelial Cell Adhesion Molecule-1 / metabolism
  • Primary Cell Culture
  • Proteoglycans / chemistry
  • Rats
  • Rats, Sprague-Dawley
  • Signal Transduction
  • Stem Cells / cytology
  • Stem Cells / drug effects*
  • Stem Cells / metabolism
  • Tissue Engineering / methods
  • Vascular Endothelial Growth Factor A / pharmacology*

Substances

  • Antigens, CD
  • Cadherins
  • Drug Combinations
  • Laminin
  • Platelet Endothelial Cell Adhesion Molecule-1
  • Proteoglycans
  • Vascular Endothelial Growth Factor A
  • cadherin 5
  • vascular endothelial growth factor A, rat
  • matrigel
  • Collagen