L-ascorbic acid 2-phosphate and fibroblast growth factor-2 treatment maintains differentiation potential in bone marrow-derived mesenchymal stem cells through expression of hepatocyte growth factor

Growth Factors. 2015 Apr;33(2):71-8. doi: 10.3109/08977194.2015.1013628. Epub 2015 Feb 25.

Abstract

l-ascorbic acid 2-phosphate (Asc-2P) acts as an antioxidant and a stimulator of hepatocyte growth factor (HGF) production. Previously, we reported that depletion of growth factors such as fibroblast growth factor (FGF)-2, epidermal growth factor (EGF), FGF-4 and HGF during serial passage could induce autophagy, senescence and down-regulation of stemness (proliferation via FGF-2/-4 and differentiation via HGF). In this study, we investigated the proliferation and differentiation potential of BMSCs by FGF-2 and Asc-2P. Co-treatment with FGF-2 and Asc-2P induced optimal proliferation of BMSCs and increased the accumulation rate of BMSC numbers during a 2-month culture period. Moreover, differentiation potential was maintained by co-treatment with FGF-2 and Asc-2P via HGF expression. Adipogenic differentiation potential by FGF-2 and Asc-2P was dramatically suppressed by c-Met inhibitors (SU11274). These data suggest that co-treatment with FGF-2 and Asc-2P would be beneficial in obtaining BMSCs that possess "stemness" during long-term culture.

Keywords: Bone marrow-derived mesenchymal stem cell; fibroblast growth factor-2; hepatocyte growth factor; l-ascorbic acid 2-phosphate; stemness.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adipocytes / cytology
  • Adult
  • Ascorbic Acid / administration & dosage
  • Ascorbic Acid / analogs & derivatives*
  • Autophagy
  • Bone Marrow Cells / drug effects*
  • Cell Differentiation
  • Cell Proliferation
  • Cells, Cultured
  • Cellular Senescence
  • Fibroblast Growth Factor 2 / administration & dosage*
  • Healthy Volunteers
  • Hepatocyte Growth Factor / metabolism*
  • Humans
  • Mesenchymal Stem Cells / drug effects*
  • Reactive Oxygen Species / metabolism
  • Young Adult

Substances

  • HGF protein, human
  • Reactive Oxygen Species
  • Fibroblast Growth Factor 2
  • ascorbate-2-phosphate
  • Hepatocyte Growth Factor
  • Ascorbic Acid