Emerging methods for preparing iPS cells

Susumu Miyazaki, Hirofumi Yamamoto, Norikatsu Miyoshi, Hidekazu Takahashi, Yozo Suzuki, Naotsugu Haraguchi, Hideshi Ishii, Yuichiro Doki, Masaki Mori

Research output: Contribution to journalArticle

27 Citations (Scopus)

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.

Original languageEnglish
Article numberhys108
Pages (from-to)773-779
Number of pages7
JournalJapanese journal of clinical oncology
Volume42
Issue number9
DOIs
Publication statusPublished - Sep 1 2012
Externally publishedYes

Fingerprint

Induced Pluripotent Stem Cells
Acids
Regenerative Medicine
Neoplasms
Transfection
Bioethical Issues
Transcription Factors
Viruses
myc Genes
Graft Rejection
Embryonic Stem Cells
Biomedical Research
Carcinogenesis
Fibroblasts
Genome
Mutation
Genes

All Science Journal Classification (ASJC) codes

  • Oncology
  • Radiology Nuclear Medicine and imaging
  • Cancer Research

Cite this

Miyazaki, S., Yamamoto, H., Miyoshi, N., Takahashi, H., Suzuki, Y., Haraguchi, N., ... Mori, M. (2012). Emerging methods for preparing iPS cells. Japanese journal of clinical oncology, 42(9), 773-779. [hys108]. https://doi.org/10.1093/jjco/hys108

Emerging methods for preparing iPS cells. / Miyazaki, Susumu; Yamamoto, Hirofumi; Miyoshi, Norikatsu; Takahashi, Hidekazu; Suzuki, Yozo; Haraguchi, Naotsugu; Ishii, Hideshi; Doki, Yuichiro; Mori, Masaki.

In: Japanese journal of clinical oncology, Vol. 42, No. 9, hys108, 01.09.2012, p. 773-779.

Research output: Contribution to journalArticle

Miyazaki, S, Yamamoto, H, Miyoshi, N, Takahashi, H, Suzuki, Y, Haraguchi, N, Ishii, H, Doki, Y & Mori, M 2012, 'Emerging methods for preparing iPS cells', Japanese journal of clinical oncology, vol. 42, no. 9, hys108, pp. 773-779. https://doi.org/10.1093/jjco/hys108
Miyazaki S, Yamamoto H, Miyoshi N, Takahashi H, Suzuki Y, Haraguchi N et al. Emerging methods for preparing iPS cells. Japanese journal of clinical oncology. 2012 Sep 1;42(9):773-779. hys108. https://doi.org/10.1093/jjco/hys108
Miyazaki, Susumu ; Yamamoto, Hirofumi ; Miyoshi, Norikatsu ; Takahashi, Hidekazu ; Suzuki, Yozo ; Haraguchi, Naotsugu ; Ishii, Hideshi ; Doki, Yuichiro ; Mori, Masaki. / Emerging methods for preparing iPS cells. In: Japanese journal of clinical oncology. 2012 ; Vol. 42, No. 9. pp. 773-779.
@article{789d4ba03d184a53931f27ea8bca2a3f,
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.",
author = "Susumu Miyazaki and Hirofumi Yamamoto and Norikatsu Miyoshi and Hidekazu Takahashi and Yozo Suzuki and Naotsugu Haraguchi and Hideshi Ishii and Yuichiro Doki and Masaki Mori",
year = "2012",
month = "9",
day = "1",
doi = "10.1093/jjco/hys108",
language = "English",
volume = "42",
pages = "773--779",
journal = "Japanese Journal of Clinical Oncology",
issn = "0368-2811",
publisher = "Oxford University Press",
number = "9",

}

TY - JOUR

T1 - Emerging methods for preparing iPS cells

AU - Miyazaki, Susumu

AU - Yamamoto, Hirofumi

AU - Miyoshi, Norikatsu

AU - Takahashi, Hidekazu

AU - Suzuki, Yozo

AU - Haraguchi, Naotsugu

AU - Ishii, Hideshi

AU - Doki, Yuichiro

AU - Mori, Masaki

PY - 2012/9/1

Y1 - 2012/9/1

N2 - 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.

AB - 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.

UR - http://www.scopus.com/inward/record.url?scp=84865534309&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84865534309&partnerID=8YFLogxK

U2 - 10.1093/jjco/hys108

DO - 10.1093/jjco/hys108

M3 - Article

VL - 42

SP - 773

EP - 779

JO - Japanese Journal of Clinical Oncology

JF - Japanese Journal of Clinical Oncology

SN - 0368-2811

IS - 9

M1 - hys108

ER -