Transgene excision has no impact on in vivo integration of human iPS derived neural precursors Journal Article

Authors: Major, T.; Menon, J.; Auyeung, G.; Soldner, F.; Hockemeyer, D.; Jaenisch, R.; Tabar, V.
Article Title: Transgene excision has no impact on in vivo integration of human iPS derived neural precursors
Abstract: The derivation of induced human pluripotent stem cells (hiPS) has generated significant enthusiasm particularly for the prospects of cell-based therapy. But there are concerns about the suitability of iPS cells for in vivo applications due in part to the introduction of potentially oncogenic transcription factors via viral vectors. Recently developed lentiviral vectors allow the excision of viral reprogramming factors and the development of transgene-free iPS lines. However it is unclear if reprogramming strategy has an impact on the differentiation potential and the in vivo behavior of hiPS progeny. Here we subject viral factor-free, c-myc-free and conventionally reprogrammed four-factor human iPS lines to a further challenge, by analyzing their differentiation potential along the 3 neural lineages and over extended periods of time in vitro, as well as by interrogating their ability to respond to local environmental cues by grafting into the striatum. We demonstrate similar and efficient differentiation into neurons, astrocytes and oligodendrocytes among all hiPS and human ES line controls. Upon intracranial grafting in the normal rat (Sprague Dawley), precursors derived from all hiPS lines exhibited good survival and response to environmental cues by integrating into the subventricular zone, acquiring phenotypes typical of type A, B or C cells and migrating along the rostral migratory stream into the olfactory bulb. There was no teratoma or other tumor formation 12 weeks after grafting in any of the 26 animals used in the study. Thus neither factor excision nor persistence of c-myc impact the behavior of hiPS lines in vivo. © 2011 Major et al.
Keywords: controlled study; human cell; nonhuman; cell proliferation; animal cell; phenotype; animal tissue; cell survival; cell function; animal experiment; astrocyte; stem cell transplantation; subventricular zone; in vitro study; cell lineage; animalia; molecular cloning; cell transformation; myc protein; rat; progeny; transgene; cell migration; fibroblast; cell therapy; cell regeneration; pluripotent stem cell; ips; rattus; immunosuppressive treatment; cell activation; nerve cell differentiation; cell activity; cyclosporin; brain region; cell transplantation; derivatization; nuclear reprogramming; corpus striatum; olfactory bulb; virus protein; virus vector; oligodendroglia; brain nerve cell
Journal Title: PLoS ONE
Volume: 6
Issue: 9
ISSN: 1932-6203
Publisher: Public Library of Science  
Date Published: 2011-09-22
Start Page: e24687
Language: English
DOI: 10.1371/journal.pone.0024687
PROVIDER: scopus
PMCID: PMC3178523
PUBMED: 21961042
Notes: --- - "Export Date: 2 November 2011" - "Source: Scopus"
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MSK Authors
  1. Viviane S Tabar
    123 Tabar
  2. Tamara Major
    4 Major
  3. Jayanthi Menon
    7 Menon