Trophism of neural progenitor cells to embryonic stem cells: Neural induction and transplantation in a mouse ischemic stroke model

Pan Fong Shu, Sze Tsang Kam, Amy Bik Wan Chan, Gang Lu, Sang Poon Wai, Karen Li, Larry William Baum, Keung Ng Ho

    Research output: Contribution to journalArticle

    23 Scopus citations

    Abstract

    Embryonic stem cell (ESC)-derived products have emerged as a promising cell source for neuroregeneration. C17.2 neural precursor cells were noted to express genes of neurotrophins and neuroprotective factors and to be enable to enhance proliferation, neuritogenesis, and differentiation of SH-SY5Y and SK-NAS neuroblasts, suggesting their neurotrophic potential. We used C17.2 cells as neurotrophic chaperones to induce ESCs, D3, and E14TG2a into neural lineage cells. Significantly greater numbers of Sox-2+, Musashi-1 +, and nestin+ neurospheres developed in non-contact cocultures than in cultures of ESCs without C17.2 support or with 50% conditioned medium after 8 days. Immunoreactivity of the neuronal, astrocytic and oligodendrocytic markers was evident in cultures further differentiated for 10 days. Expression of Pax-6, Otx-1, and Nurr-1 genes suggested neuroectodermal precursors in products encompassing neural stem cells, dopaminergic neurons, astrocytes, and oligodendrocytes. α-Fetoprotein, GATA-4, Brachyury, Nkx-2.5, and Myf-5 genes were not detected, indicating any mesodermal and endodermal cells. However, weak expression of Oct-4 was noted. Behavioral assessment of ischemic mice 2 weeks after transplantation revealed significant improvement in cognitive function compared with that in ischemic sham-operated mice. Tracking bromodeoxyuridine-labeled products demonstrated that mostly implanted cells were localized along the needle track of the injection in the brain parenchyma, whereas some migrated to the striatum, cortex, nerve fiber bundle of the corpus callosum, and hippocampus in the ipsilateral hemisphere. One episode (of 22) of teratoma development was noted. Data from this study suggest a paradigm of trophism of neural progenitor cells for induction of ESCs into neural lineage cells.

    Original languageEnglish (US)
    Pages (from-to)1851-1862
    Number of pages12
    JournalJournal of neuroscience research
    Volume85
    Issue number9
    DOIs
    StatePublished - Jul 1 2007

    Keywords

    • C17.2 cells
    • ES cells
    • Ischemic stroke
    • Neural differentiation
    • Transplantation

    ASJC Scopus subject areas

    • Cellular and Molecular Neuroscience

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