https://www.ncbi.nlm.nih.gov/pubmed/22753232
Abstract
Human
embryonic stem cell-derived neuronal progenitors (hNPs) provide a
potential source for cellular replacement following neurodegenerative
diseases. One of the greatest challenges for future neuron replacement
therapies will be to control extensive cell proliferation and stimulate
cell migration of transplanted cells. The doublecortin (DCX) gene
encodes the protein DCX, a microtubule-associated protein essential for
the migration of neurons in the human brain. In this study, we tested
whether increasing the expression of DCX in hNPs would favorably alter
their proliferation and migration. Migration and proliferation of hNPs
was compared between hNPs expressing a bicistronic DCX/IRES-GFP
transgene and those expressing a green fluorescent protein (GFP)
transgene introduced by piggyBac-mediated transposition. The
DCX-transfected hNPs showed a significant decrease in their
proliferation and migrated significantly further on two different
substrates, Matrigel and brain slices. Additionally, a dense network of
nestin-positive (+) and vimentin+ fibers were found to extend from
neurospheres transplanted onto brain slices, and this fiber growth was
increased from neurospheres containing DCX-transfected hNPs. In summary,
our results show that increased DCX expression inhibits proliferation
and promotes migration of hNPs.
Copyright © 2012 AlphaMed Press.
- PMID:
- 22753232
- PMCID:
- PMC3951429
- DOI:
- 10.1002/stem.1162
- [PubMed - indexed for MEDLINE]
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