Inducing functional radial glia-like progenitors from cortical astrocyte cultures using micropatterned PMMA.
2012
Radial glia cells (RGC) are multipotent progenitors that generate neurons and glia during CNS development,
and which also served as substrate for neuronal migration. After a lesion, reactive glia are the
main contributor to CNS regenerative blockage, although some reactive astrocytes are also able to dedifferentiate
in situ into radial glia-like cells (RGLC), providing beneficial effects in terms of CNS
recovery. Thus, the identification of substrate properties that potentiate the ability of astrocytes to
transform into RGLC in response to a lesion might help in the development of implantable devices that
improve endogenous CNS regeneration. Here we demonstrate that functional RGLC can be induced from
in vitro matured astrocytes by using a precisely-sized micropatterned PMMA grooved scaffold, without
added soluble or substrate adsorbed biochemical factors. RGLC were extremely organized and aligned on
2 mm line patterned PMMA and, like their embryonic counterparts, express nestin, the neuron-glial
progenitor marker Pax6, and also proliferate, generate different intermediate progenitors and support
and direct axonal growth and neuronal migration. Our results suggest that the introduction of line
patterns in the size range of the RGC processes in implantable scaffolds might mimic the topography of
the embryonic neural stem cell niche, driving endogenous astrocytes into an RGLC phenotype, and thus
favoring the regenerative response in situ.
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