Pleiotrophin is involved in the amniotic epithelial cell-induced differentiation of human umbilical cord blood-derived mesenchymal stem cells into dopaminergic neuron-like cells

Neurosci Lett. 2013 Feb 28:539:86-91. doi: 10.1016/j.neulet.2013.01.046. Epub 2013 Feb 8.

Abstract

We have reported that human umbilical cord blood-derived mesenchymal stem cells (hUCB-MSCs) are capable of differentiating into dopaminergic (DA) neuron-like cells upon being induced by amniotic epithelial cells (AECs). However, what factor(s) is involved in the differentiation process has not been explored out thoroughly. Because pleiotrophin (PTN) is known to exert important trophic effects on DA neurons, in the present study, we investigated whether PTN is released by AECs and whether it is involved in the differentiation of hUCB-MSCs into DA neuron-like cells. The expression and secretion of PTN by AECs were detected by immunofluorescence, RT-PCR and ELISA. The hUCB-MSCs were isolated and treated with AEC-conditioned medium (ACM) or recombinant human PTN. Compared to the controls, a higher proportion of treated cells differentiated into DA neuron-like cells, indicated by the increased expression of TH and DAT and the increased dopamine content. These results indicate that PTN released by AECs acts as a synergetic factor with other neurotrophic factors and is involved in the differentiation of hUCB-MSCs into DA neuron-like cells. We suggest that ACM, which contains PTN and other neurotrophic factors, could potentially be used as an agent to promote the differentiation of DA neuron-like cells from hUCB-MSCs for cell therapy of Parkinson's disease without creating legal or ethical issues.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amnion / cytology*
  • Amnion / metabolism
  • Carrier Proteins / metabolism*
  • Carrier Proteins / pharmacology
  • Cell Differentiation
  • Cells, Cultured
  • Culture Media, Conditioned
  • Cytokines / metabolism*
  • Cytokines / pharmacology
  • Dopaminergic Neurons / cytology*
  • Dopaminergic Neurons / drug effects
  • Dopaminergic Neurons / metabolism
  • Epithelial Cells / cytology*
  • Epithelial Cells / drug effects
  • Epithelial Cells / metabolism
  • Fetal Blood / cytology*
  • Fetal Blood / metabolism
  • Humans
  • Mesenchymal Stem Cells / cytology*
  • Mesenchymal Stem Cells / drug effects
  • Mesenchymal Stem Cells / metabolism
  • Recombinant Proteins / pharmacology

Substances

  • Carrier Proteins
  • Culture Media, Conditioned
  • Cytokines
  • Recombinant Proteins
  • pleiotrophin