Characterization of Adult Human Neural Progenitor Cell Differentiation In Vitro and In Vivo

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.