Transgene Excision Has No Impact on In Vivo Integration of Human iPS Derived Neural Precursors
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 transcr...
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| Format: | Article |
| Language: | en_US |
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Public Library of Science
2012
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| Online Access: | http://hdl.handle.net/1721.1/69089 |
| _version_ | 1826189022165204992 |
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| author | Major, Tamara Menon, Jayanthi Auyeung, Gordon Soldner, Frank Hockemeyer, Dirk Jaenisch, Rudolf Tabar, Viviane |
| author2 | Massachusetts Institute of Technology. Department of Biology |
| author_facet | Massachusetts Institute of Technology. Department of Biology Major, Tamara Menon, Jayanthi Auyeung, Gordon Soldner, Frank Hockemeyer, Dirk Jaenisch, Rudolf Tabar, Viviane |
| author_sort | Major, Tamara |
| collection | MIT |
| description | 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. |
| first_indexed | 2024-09-23T08:08:38Z |
| format | Article |
| id | mit-1721.1/69089 |
| institution | Massachusetts Institute of Technology |
| language | en_US |
| last_indexed | 2024-09-23T08:08:38Z |
| publishDate | 2012 |
| publisher | Public Library of Science |
| record_format | dspace |
| spelling | mit-1721.1/690892022-09-23T11:10:21Z Transgene Excision Has No Impact on In Vivo Integration of Human iPS Derived Neural Precursors Major, Tamara Menon, Jayanthi Auyeung, Gordon Soldner, Frank Hockemeyer, Dirk Jaenisch, Rudolf Tabar, Viviane Massachusetts Institute of Technology. Department of Biology Whitehead Institute for Biomedical Research Jaenisch, Rudolf Soldner, Frank Hockemeyer, Dirk Jaenisch, Rudolf 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. United States. National Institutes of Health New York State Stem Cell Science National Institute of Neurological Disorders and Stroke (U.S.) Starr Foundation (Tri-Institutional Starr Stem Cell Scholars Fellowship) 2012-02-10T19:48:03Z 2012-02-10T19:48:03Z 2011-09 2011-06 Article http://purl.org/eprint/type/JournalArticle 1932-6203 http://hdl.handle.net/1721.1/69089 Major, Tamara et al. “Transgene Excision Has No Impact on In Vivo Integration of Human iPS Derived Neural Precursors.” Ed. Debra L. Silver. PLoS ONE 6.9 (2011): e24687. Web. 10 Feb. 2012. en_US http://dx.doi.org/10.1371/journal.pone.0024687 PLoS ONE Creative Commons Attribution http://creativecommons.org/licenses/by/2.5/ application/pdf Public Library of Science PLoS |
| spellingShingle | Major, Tamara Menon, Jayanthi Auyeung, Gordon Soldner, Frank Hockemeyer, Dirk Jaenisch, Rudolf Tabar, Viviane Transgene Excision Has No Impact on In Vivo Integration of Human iPS Derived Neural Precursors |
| title | Transgene Excision Has No Impact on In Vivo Integration of Human iPS Derived Neural Precursors |
| title_full | Transgene Excision Has No Impact on In Vivo Integration of Human iPS Derived Neural Precursors |
| title_fullStr | Transgene Excision Has No Impact on In Vivo Integration of Human iPS Derived Neural Precursors |
| title_full_unstemmed | Transgene Excision Has No Impact on In Vivo Integration of Human iPS Derived Neural Precursors |
| title_short | Transgene Excision Has No Impact on In Vivo Integration of Human iPS Derived Neural Precursors |
| title_sort | transgene excision has no impact on in vivo integration of human ips derived neural precursors |
| url | http://hdl.handle.net/1721.1/69089 |
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