A brief very-low oxygen tension regimen is sufficient for the early chondrogenic commitment of human adipose-derived mesenchymal stem cells

Adv Med Sci. 2021 Mar;66(1):98-104. doi: 10.1016/j.advms.2020.12.005. Epub 2021 Jan 15.

Abstract

Purpose: The aim of this study was to evaluate the effects exerted over chondrogenic commitment of human adipose-derived mesenchymal stem cells (ADSCs) by a very low oxygen tension (<1% pO2).

Materials/methods: Cell morphology, mRNA levels of chondrocyte-specific marker genes and the involvement of p38 MAPK signalling were monitored in human ADSCs under a very low oxygen tension.

Results: Cell morphology was significantly changed after two days of hypoxic preconditioning when they featured as elongated spindle-shaped cells. SRY-box containing gene 9, aggrecan and collagen type II mRNA levels were enhanced under severe hypoxic culture conditions. Moreover, the inhibition of p38 MAPK resulted in a substantial reduction in transcription of the above-mentioned specific genes, proving the pivotal role of this pathway in the transcriptional regulation of chondrogenesis.

Conclusions: Here, we propose a protocol showing the early commitment of stem cells towards the chondrogenic phenotype in only 2 days of culture via a very low hypoxic environment, in the absence of growth factors added in the culture medium.

Keywords: Adipose-derived mesenchymal stem cells; Chondrogenic commitment; Hypoxia; Translational medicine; p38 MAPK.

MeSH terms

  • Adult
  • Cell Differentiation
  • Cell Proliferation
  • Cells, Cultured
  • Chondrocytes / cytology*
  • Chondrocytes / drug effects
  • Chondrocytes / metabolism
  • Chondrogenesis*
  • Female
  • Gene Expression Regulation / drug effects*
  • Humans
  • Mesenchymal Stem Cells / cytology*
  • Mesenchymal Stem Cells / drug effects
  • Mesenchymal Stem Cells / metabolism
  • Oxygen / pharmacology*

Substances

  • Oxygen