The differentiation effect of bone morphogenetic protein (BMP) on human amniotic epithelial stem cells to express ectodermal lineage markers

Cell Tissue Res. 2021 Feb;383(2):751-763. doi: 10.1007/s00441-020-03280-z. Epub 2020 Sep 22.

Abstract

Stem cells are a promising tool for treatment of a variety of degenerative diseases. Human amniotic epithelial stem cells (hAECs) have desirable and unique characteristics that make them a proper candidate for cell therapy. In this study, we have investigated the effects of BMP-4 (bone morphogenetic protein-4) and its inhibition on differentiation of AECs into ectodermal lineages. Analysis of AEC-derived ectodermal lineages (neurons and keratinocytes) was performed by using flow cytometry technique for Map2 and β-tubulin (as neuron markers), Olig2 and MBP (as oligodendrocyte markers), and K14 and K10 (as keratinocyte markers). The results of this study illustrated that noggin (as BMP antagonist), BMP4, and both BMP4 and heparin (together or separately) increased neural and keratinocyte marker expression, respectively. The expression of markers MAP2, olig2, and K14 in hAECs has been significantly decreased 21 days after exposure to differentiation medium (without growth factors) compared with isolation day, which supports the hypothesis that AECs can be dedifferentiated into pluripotent cells. Moreover, activation and inhibition of BMP signaling have no effects on viability of hAECs. The results of this study showed that BMP signaling and its inhibition are the key factors for ectodermal lineage differentiation of amnion-derived stem cells.

Keywords: Amniotic epithelial cell; BMP4; Differentiation; Glia; Keratinocyte; Neuronal lineage.

MeSH terms

  • Amnion / cytology*
  • Biomarkers / metabolism*
  • Bone Morphogenetic Proteins / pharmacology*
  • Cell Dedifferentiation / drug effects
  • Cell Differentiation / drug effects*
  • Cell Lineage*
  • Cell Separation
  • Cell Survival / drug effects
  • Cells, Cultured
  • Ectoderm / cytology*
  • Epithelial Cells / cytology*
  • Epithelial Cells / drug effects
  • Epithelial Cells / metabolism
  • Humans
  • Keratinocytes / cytology
  • Keratinocytes / drug effects
  • Keratinocytes / metabolism
  • Stem Cells / cytology*
  • Stem Cells / drug effects
  • Stem Cells / metabolism
  • Tubulin / metabolism

Substances

  • Biomarkers
  • Bone Morphogenetic Proteins
  • Tubulin