title: Emerging methods for preparing iPS cells.
abstract: In 1998, human embryonic stem cells were first generated and were expected to contribute greatly to regenerative medicine. However, when medical treatments were performed using human embryonic stem cells, there were problems, such as transplant rejection, as well as bioethical issues. Induced pluripotent stem cells were generated from mouse and human fibroblasts in 2006 and 2007 by introducing four transcription factors (Oct3/4, Sox2, c-Myc and Klf4). This process was defined as direct reprogramming, and induced pluripotent stem cells were better tolerated. Although induced pluripotent stem cells have contributed greatly to biomedical research and regenerative medicine, high tumorigenic potential is still a critical problem due to the introduction of the oncogene c-Myc and reprogramming with a virus vector. To address this, we reprogrammed somatic cells by transfection with microribonucleic acids to avoid using virus vectors for genomic integration into the host genome. We found that it was possible to reprogram mouse and human cells to pluripotency by direct transfection of three mature microribonucleic acids (mir-200c, -302s and -369s) with increased expression levels in embryonic stem cells and induced pluripotent stem cells. The microribonucleic acid-induced pluripotent stem cells have a reduced risk of mutations and tumorigenesis. Our laboratory also introduced four transcription factors (Oct3/4, Sox2, c-Myc and Klf4) into cancer cells, generating induced pluripotent cancer cells that exhibited strikingly less malignant features, suggesting the possibility of a novel type of cancer therapy. However, the gene transduction method is not yet safe for clinical applications, due to a genomic integration that may cause tumor formation. We are currently investigating the reprogramming method using microribonucleic acids in cancer cells to develop a very safe, highly efficient and highly complete reprogramming for clinical applications.
authors: Department of Gastroenterological Surgery, Osaka University, Graduate School of Medicine, Yamadaoka 2-2, Suita, Osaka 565-0871, Japan.
authors: Susumu
authors: S
authors: Miyazaki
authors: Hirofumi
authors: H
authors: Yamamoto
authors: Norikatsu
authors: N
authors: Miyoshi
authors: Hidekazu
authors: H
authors: Takahashi
authors: Yozo
authors: Y
authors: Suzuki
authors: Naotsugu
authors: N
authors: Haraguchi
authors: Hideshi
authors: H
authors: Ishii
authors: Yuichiro
authors: Y
authors: Doki
authors: Masaki
authors: M
authors: Mori
mesh_terms: D000818:Animals; D065150:Cellular Reprogramming; D016259:Genes, myc; D015316:Genetic Therapy / Q000379:methods*; D005822:Genetic Vectors; D006801:Humans; D057026:Induced Pluripotent Stem Cells; D000090062:Kruppel-Like Factor 4; D051741:Kruppel-Like Transcription Factors / Q000235:genetics; D016086:Lentivirus; D051379:Mice; D035683:MicroRNAs; D009369:Neoplasms / Q000235:genetics* / Q000628:therapy*; D014411:Neoplastic Stem Cells; D050814:Octamer Transcription Factor-3 / Q000235:genetics; D016271:Proto-Oncogene Proteins c-myc / Q000235:genetics; D012190:Retroviridae; D055748:SOXB1 Transcription Factors / Q000235:genetics; D014157:Transcription Factors / Q000235:genetics*; D014161:Transduction, Genetic / Q000379:methods; D014162:Transfection / Q000379:methods*
chemical_list: C000715467:KLF4 protein, human; C000715468:Klf4 protein, mouse; D000090062:Kruppel-Like Factor 4; D051741:Kruppel-Like Transcription Factors; C533896:MIRN200 microRNA, human; C560308:MIRN369 microRNA, human; C489427:MYC protein, human; D035683:MicroRNAs; C489428:Myc protein, mouse; D050814:Octamer Transcription Factor-3; C494173:POU5F1 protein, human; C494174:Pou5f1 protein, mouse; D016271:Proto-Oncogene Proteins c-myc; C527782:SOX2 protein, human; D055748:SOXB1 Transcription Factors; C527783:Sox2 protein, mouse; D014157:Transcription Factors