Cobalt chloride improves angiogenic potential of CD133+ cells

Front Biosci (Landmark Ed). 2012 Jun 1;17(6):2247-58. doi: 10.2741/4048.

Abstract

Umbilical cord blood-derived CD133+ cells exhibit the ability to differentiate into endothelial cells and induce new blood vessel growth. Hypoxia-inducible factor-1 (HIF-1), a regulator of hypoxia or the hypoxia-mimetic agent response, actives the SDF-1/CXCR4 signaling pathway and thus plays an important role in angiogenesis in-vivo. In this study we aim to investigate whether CD133+ cells enhance angiogenic ability through hypoxia or CoCl2 in vitro. The CD133+ cells were cultured in normoxia (20 Percent O2), hypoxia (10 Percent O2, 3 Percent O2), or in various concentrations of CoCl2 (50 microM/L, 100 microM/L, 200 microM/L) and subjected to in vitro flow cytometric analysis, tubule formation, as well as migration and proliferation assays. The results demonstrate that both environmental hypoxia and CoCl2 induced hypoxia result in significantly increased CD133+ cell migration, proliferation, and tubule-like structure formation compared with normoxia culture conditions. The HIF-1a, SDF-1, and VEGF protein and gene expression level in conditions of hypoxia is higher than that found in normaxia conditions. Collectively, these data suggest that angiogenic potential of CD133+ cells is influenced by hypoxia or a hypoxia mimetic agent in vitro.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • AC133 Antigen
  • Antigens, CD / metabolism*
  • Cell Hypoxia / drug effects
  • Cell Movement / drug effects
  • Cell Proliferation / drug effects
  • Chemokine CXCL12 / genetics
  • Chemokine CXCL12 / metabolism
  • Cobalt / pharmacology*
  • Endothelial Cells / cytology*
  • Endothelial Cells / drug effects*
  • Endothelial Cells / immunology
  • Endothelial Cells / metabolism
  • Fetal Blood / cytology
  • Fibroblast Growth Factors / genetics
  • Fibroblast Growth Factors / metabolism
  • Gene Expression / drug effects
  • Glycoproteins / metabolism*
  • Humans
  • Hypoxia-Inducible Factor 1, alpha Subunit / genetics
  • Hypoxia-Inducible Factor 1, alpha Subunit / metabolism
  • In Vitro Techniques
  • Neovascularization, Physiologic / drug effects
  • Peptides / metabolism*
  • RNA, Messenger / genetics
  • RNA, Messenger / metabolism
  • Stem Cells / cytology*
  • Stem Cells / drug effects*
  • Stem Cells / immunology
  • Stem Cells / metabolism
  • Vascular Endothelial Growth Factor A / genetics
  • Vascular Endothelial Growth Factor A / metabolism

Substances

  • AC133 Antigen
  • Antigens, CD
  • CXCL12 protein, human
  • Chemokine CXCL12
  • Glycoproteins
  • HIF1A protein, human
  • Hypoxia-Inducible Factor 1, alpha Subunit
  • PROM1 protein, human
  • Peptides
  • RNA, Messenger
  • VEGFA protein, human
  • Vascular Endothelial Growth Factor A
  • Cobalt
  • Fibroblast Growth Factors
  • cobaltous chloride