Characterization of Adult Human Neural Progenitor Cell Differentiation In Vitro and In Vivo
Date
2011-05
Authors
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Journal ISSN
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Publisher
University of Delaware
Abstract
The stem cell cancer hypothesis has suggested that stem and progenitor
cells may be the likely source of accumulation of oncogenic factors that lead to
specific cancer cell types. Additional insight into this mechanism may be garnered by
studying the differentiation of adult human neural progenitor (AHNP) cells and the
role of L1, the cell adhesion molecule that has been previously shown to increase
glioma cell motility and invasion. Previous studies have shown that adult human
neural progenitor cells can differentiate into neurons and astrocytes both in vitro and
in vivo. This also suggests that these cells can potentially be used to treat individuals
with nervous system disorders that specifically involve neurons and astrocytes. No
work had shown that oligodendrocytes had been isolated in culture or in vivo.
Immunocytochemical characterization of adult human neural progenitors
was performed in order to assess L1 levels and the progenitor nature of the cells being
cultured. Vimentin immunostaining suggested that the cells were expressing
progenitor markers during in vitro experiments. The astrocyte marker, glial fibrillary
acidic protein, was also expressed in cell culture. L1 ectodomain was detected in the
progenitor cells, as well as Pax-6 transcription factor for L1. In co-culturing
experiments using both monolayer co-cultures and aggregate co-cultures, the AHNPs
were cultured with chick embryo brain cells and evaluated for differentiation.
Monolayer co-cultures proved to be difficult as AHNPs minimally interacted with the
chick embryo brain cells. Aggregate co-cultures improved cell-to-cell interactions and
positive oligodendrocyte immunostaining was found.
Though improvements to the co-culturing methods can be developed, the
AHNPs did show a potential plasticity to induce differentiation. The progenitor cells
were cultured without growth factors and neuronal markers were detected.
Overexpression of L1 ectodomain in the AHNPs did not produce any changes, though
the future investigation of cell motility and invasion will require understand if any L1-
mediated signaling is involved.
Description
Keywords
Adult human neural progenitor (AHNP), Stem cells, Progenitor cells, Stem cell cancer hypothesis