title: Generation of induced pluripotent stem cells from virus-free in vivo reprogramming of BALB/c mouse liver cells.
abstract: The in vivo cell reprogramming of terminally differentiated somatic cells to a pluripotent state by the ectopic expression of defined transcription factors has been previously shown in the BALB/c mouse liver upon plasmid DNA injection with no teratoma formation in the host tissue. Here, we hypothesized that the reprogrammed cells could be extracted from the tissue and cultured in vitro. We called these cells in vivo induced pluripotent stem (i(2)PS) cells because they showed pluripotent characteristics equivalent to a standard mouse ES cell line (E14TG2A). The pluripotent character of i(2)PS cells was determined by a battery of morphological, molecular and functional assays, including their contribution to adult tissues of chimeric mice upon blastocyst injection. These observations further confirm that terminally differentiated somatic cells in wild type, adult animals can be reprogrammed in vivo using virus-free methodologies. The reprogrammed cells can generate in vitro stem cell colonies that exhibit pluripotency similar to ES cells with numerous implications for the application of in vivo reprogramming for tissue regenerative purposes.
authors.affiliation: Nanomedicine Lab, Faculty of Medical and Human Sciences, University of Manchester, AV Hill Building, Upper Brook Street, Manchester M13 9PT, United Kingdom; UCL School of Life & Medical Sciences, University College London, Brunswick Square, WC1N 1AX London, United Kingdom.
authors.forename: Irene
authors.initials: I
authors.lastname: de Lázaro
authors.affiliation: Nanomedicine Lab, Faculty of Medical and Human Sciences, University of Manchester, AV Hill Building, Upper Brook Street, Manchester M13 9PT, United Kingdom; UCL School of Life & Medical Sciences, University College London, Brunswick Square, WC1N 1AX London, United Kingdom.
authors.forename: Cyrill
authors.initials: C
authors.lastname: Bussy
authors.affiliation: UCL School of Life & Medical Sciences, University College London, Brunswick Square, WC1N 1AX London, United Kingdom.
authors.forename: Açelya
authors.initials: A
authors.lastname: Yilmazer
authors.affiliation: Transgenic Facility, Faculty of Life Sciences, University of Manchester, Upper Brook Street, Manchester M13 9PT, United Kingdom.
authors.forename: Maj Simonsen
authors.initials: MS
authors.lastname: Jackson
authors.affiliation: Transgenic Facility, Faculty of Life Sciences, University of Manchester, Upper Brook Street, Manchester M13 9PT, United Kingdom.
authors.forename: Neil E
authors.initials: NE
authors.lastname: Humphreys
authors.affiliation: Nanomedicine Lab, Faculty of Medical and Human Sciences, University of Manchester, AV Hill Building, Upper Brook Street, Manchester M13 9PT, United Kingdom; UCL School of Life & Medical Sciences, University College London, Brunswick Square, WC1N 1AX London, United Kingdom. Electronic address: kostas.kostarelos@manchester.ac.uk.
authors.forename: Kostas
authors.initials: K
authors.lastname: Kostarelos
mesh_terms: D000818:Animals; D018929:Cell Culture Techniques; D002460:Cell Line; D065150:Cellular Reprogramming; D002678:Chimera; D004247:DNA / Q000008:administration & dosage / Q000235:genetics; D053595:Embryonic Stem Cells / Q000166:cytology / Q000378:metabolism; D022781:Hepatocytes / Q000166:cytology* / Q000378:metabolism; D057026:Induced Pluripotent Stem Cells / Q000166:cytology* / Q000378:metabolism; D008807:Mice, Inbred BALB C; D010957:Plasmids / Q000008:administration & dosage / Q000235:genetics; D059467:Transcriptome
chemical_list: D004247:DNA
keywords: Induced pluripotent stem cells; In vivo reprogramming; Pluripotency; Virus-free