title: Generation of clinically relevant "induced pluripotent stem" (iPS) cells.
abstract: Proviral expression of early development genes Oct4 and Sox2, in concert with cMyc and Klf4 or Nanog and Lin28, can induce differentiated cells to adopt morphological and functional characteristics of pluripotency indistinguishable from embryonic stem cells. Termed induced pluripotent stem (iPS) cells, in mice the pluripotency of these cells was confirmed by altered gene/surface antigen expression, remodeling of the epigenome, ability to contribute to embryonic lineages following blastocyst injection and commitment to all three germ layers in teratomas and liveborn chimeras. Importantly, in vitro directed differentiation of iPS cells yield cells capable of treating mouse models of humanized disease. Despite these impressive results, iPS cell conversion is frustratingly inefficient. Also, the unpredictable and random mutagenesis imposed on the host cell genome, inherent with integrative viral methodologies, continues to hamper use of these cells in a therapeutic setting. This has initiated exploration of non-integrating strategies for generating iPS cells. Here, we review mechanisms that drive conversion of somatic cells to iPS cells and the strategies adopted to circumvent integrative viral strategies. Finally, we discuss practical, ethical and legal considerations that require addressing before iPS cells can realize their potential as patient-specific cells for treatment of degenerative disease.
authors.affiliation: Reprogramming and Stem Cell Laboratory, Monash Institute of Medical Research, Monash University, Clayton, VIC, Australia.
authors.forename: Corey
authors.initials: C
authors.lastname: Heffernan
authors.forename: Huseyin
authors.initials: H
authors.lastname: Sumer
authors.forename: Paul J
authors.initials: PJ
authors.lastname: Verma
mesh_terms: D000818:Animals; D002454:Cell Differentiation; D002478:Cells, Cultured; D065150:Cellular Reprogramming; D018507:Gene Expression Regulation, Developmental; D005822:Genetic Vectors; D005838:Genotype; D018398:Homeodomain Proteins / Q000235:genetics / Q000378:metabolism; D006801:Humans; D057026:Induced Pluripotent Stem Cells / Q000502:physiology* / Q000637:transplantation; D000090062:Kruppel-Like Factor 4; D051741:Kruppel-Like Transcription Factors / Q000235:genetics / Q000378:metabolism; D050814:Octamer Transcription Factor-3 / Q000235:genetics / Q000378:metabolism; D010641:Phenotype; D016271:Proto-Oncogene Proteins c-myc / Q000235:genetics / Q000378:metabolism; D016601:RNA-Binding Proteins / Q000235:genetics / Q000378:metabolism; D055748:SOXB1 Transcription Factors / Q000235:genetics / Q000378:metabolism; D033581:Stem Cell Transplantation / Q000009:adverse effects / Q000941:ethics; D014162:Transfection
chemical_list: D018398:Homeodomain Proteins; C000715467:KLF4 protein, human; C000715468:Klf4 protein, mouse; D000090062:Kruppel-Like Factor 4; D051741:Kruppel-Like Transcription Factors; D050814:Octamer Transcription Factor-3; D016271:Proto-Oncogene Proteins c-myc; D016601:RNA-Binding Proteins; D055748:SOXB1 Transcription Factors