Enhanced angiogenic activity of dimethyloxalylglycine-treated canine adipose tissue-derived mesenchymal stem cells

J Vet Med Sci. 2019 Dec 5;81(11):1663-1670. doi: 10.1292/jvms.19-0337. Epub 2019 Oct 2.

Abstract

The paracrine function of mesenchymal stem cells (MSCs) during transplantation has been recently studied due to its poor differentiation ratio. Dimethyloxalylglycine (DMOG) has been used to promote angiogenesis in experimental animal models, however, comparable approaches for canine MSCs are not sufficient. In the present study, we assessed whether DMOG improves angiogenesis in canine adipose tissue-derived mesenchymal stem cells (cAT-MSCs). cAT-MSCs were treated with DMOG and their effect on angiogenesis was investigated by cell proliferation assay, western blotting, and tube formation assay. Dimethyloxalylglycine preconditioning enhanced the expression of vascular endothelial growth factor (VEGF) among pro-angiogenic factors in cAT-MSCs via hypoxia-inducible factor-1α stabilization. Dimethyloxalylglycine primed-cAT-MSC-conditioned media increased angiogenesis in human umbilical vein endothelial cells. These results suggest that DMOG conditioning of cAT-MSCs augmented the secretion of VEGF, which acted as a prominent pro-angiogenic factor during angiogenesis. DMOG-primed cAT-MSCs may have the potential to induce beneficial effects in ischemic diseases in clinical trials.

Keywords: angiogenesis; dimethyloxalylglycine; dog; mesenchymal stem cell; vascular endothelial growth factor.

MeSH terms

  • Angiogenesis Inducing Agents / metabolism
  • Animals
  • Cell Differentiation / drug effects
  • Dogs*
  • Gene Expression Regulation / drug effects
  • Glycine / analogs & derivatives*
  • Glycine / pharmacology
  • Mesenchymal Stem Cells / drug effects*
  • Neovascularization, Physiologic / drug effects*
  • RNA, Messenger / genetics
  • RNA, Messenger / metabolism

Substances

  • Angiogenesis Inducing Agents
  • RNA, Messenger
  • dimethyloxallyl glycine
  • Glycine