Meningeal cells induce dopaminergic neurons from embryonic stem cells

The European Journal of Neuroscience
Hideki HayashiJun Takahashi

Abstract

Neural induction of midbrain dopaminergic (DA) neurons from embryonic stem (ES) cells can be achieved by culturing them on a bone marrow-derived stromal cell line, PA6, which possesses stromal cell-derived inducing activity (SDIA). The mechanism of SDIA is unknown, but clinical application of ES cell transplantation requires the use of defined factors for DA neuron induction. Here, we demonstrate that meningeal cells harvested from the developing dura can induce DA neuron differentiation from mouse and human ES cells, as assessed by midbrain DA marker expression and secretion of DA in response to potassium stimuli. Intriguingly, the inductive strength of meningeal cells depends on their developmental stage, with those harvested from embryonic day 18 embryos showing the highest activity. Among six soluble factors known to be involved in DA neuron differentiation, only Wnt-5a and transforming growth factor-beta3 were expressed by both meningeal and PA6 cells, and the expression of Wnt-5a correlated with the DA neuron induction activity of these cells. Furthermore, the induction of DA neuron differentiation by PA6 cell-conditioned medium was reversed by addition of a Wnt-5a neutralizing antibody, whereas recombinant Wnt-5a promote...Continue Reading

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Citations

Oct 31, 2012·Molecular and Cellular Biology·Lukáš ČajánekErnest Arenas
Mar 10, 2010·Regenerative Medicine·Rosemary A Fricker-Gates, Monte A Gates
Sep 9, 2008·Expert Opinion on Biological Therapy·Jinghua HaoDong-An Wang
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Sep 17, 2020·The Neuroscientist : a Review Journal Bringing Neurobiology, Neurology and Psychiatry·Ilaria DecimoFrancesco Bifari

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