Development of a High-Efficacy Reprogramming Method for Generating Human Induced Pluripotent Stem (iPS) Cells from Pathologic and Senescent Somatic Cells
Induced pluripotent stem (iPS) cells are a type of artificial pluripotent stem cell induced by the epigenetic silencing of somatic cells by the Yamanaka factors. Advances in iPS cell reprogramming technology will allow aging or damaged cells to be replaced by a patient’s own rejuvenated cells. Howev...
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doaj-7139ba41603041979a2c60c5694c399d2020-11-25T03:41:20ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672020-09-01216764676410.3390/ijms21186764Development of a High-Efficacy Reprogramming Method for Generating Human Induced Pluripotent Stem (iPS) Cells from Pathologic and Senescent Somatic CellsNaomichi Tanaka0Hidemasa Kato1Hiromi Tsuda2Yasunori Sato3Toshihiro Muramatsu4Atsushi Iguchi5Hiroyuki Nakajima6Akihiro Yoshitake7Takaaki Senbonmatsu8Department of Cardiology, International Medical Center, Saitama Medical University, Saitama 350-1298, JapanDepartment of Anatomy, Ehime University School of Medicine, Ehime 791-0295, JapanDepartment of Cardiology, International Medical Center, Saitama Medical University, Saitama 350-1298, JapanDepartment of Preventive Medicine and Public Health, Keio University School of Medicine, Tokyo 160-8582, JapanDepartment of Cardiology, International Medical Center, Saitama Medical University, Saitama 350-1298, JapanDepartment of Cardiovascular Surgery, International Medical Center, Saitama Medical University, Saitama 350-1298, JapanDepartment of Cardiovascular Surgery, International Medical Center, Saitama Medical University, Saitama 350-1298, JapanDepartment of Cardiovascular Surgery, International Medical Center, Saitama Medical University, Saitama 350-1298, JapanDepartment of Cardiology, International Medical Center, Saitama Medical University, Saitama 350-1298, JapanInduced pluripotent stem (iPS) cells are a type of artificial pluripotent stem cell induced by the epigenetic silencing of somatic cells by the Yamanaka factors. Advances in iPS cell reprogramming technology will allow aging or damaged cells to be replaced by a patient’s own rejuvenated cells. However, tissue that is senescent or pathologic has a relatively low reprogramming efficiency as compared with juvenile or robust tissue, resulting in incomplete reprogramming; iPS cells generated from such tissue types do not have sufficient differentiation ability and are therefore difficult to apply clinically. Here, we develop a new reprogramming method and examine it using myofibroblasts, which are pathologic somatic cells, from patient skin tissue and from each of the four heart chambers of a recipient heart in heart transplant surgery. By adjusting the type and amount of vectors containing transcriptional factors for iPS cell reprogramming, as well as adjusting the transfection load and culture medium, the efficiency of iPS cell induction from aged patient skin-derived fibroblasts was increased, and we successfully induced iPS cells from myocardial fibroblasts isolated from the pathologic heart of a heart transplant recipient.https://www.mdpi.com/1422-0067/21/18/6764iPS cellmyocardial fibroblastmyofibroblastsenescencepathologic stateTGF-beta |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Naomichi Tanaka Hidemasa Kato Hiromi Tsuda Yasunori Sato Toshihiro Muramatsu Atsushi Iguchi Hiroyuki Nakajima Akihiro Yoshitake Takaaki Senbonmatsu |
spellingShingle |
Naomichi Tanaka Hidemasa Kato Hiromi Tsuda Yasunori Sato Toshihiro Muramatsu Atsushi Iguchi Hiroyuki Nakajima Akihiro Yoshitake Takaaki Senbonmatsu Development of a High-Efficacy Reprogramming Method for Generating Human Induced Pluripotent Stem (iPS) Cells from Pathologic and Senescent Somatic Cells International Journal of Molecular Sciences iPS cell myocardial fibroblast myofibroblast senescence pathologic state TGF-beta |
author_facet |
Naomichi Tanaka Hidemasa Kato Hiromi Tsuda Yasunori Sato Toshihiro Muramatsu Atsushi Iguchi Hiroyuki Nakajima Akihiro Yoshitake Takaaki Senbonmatsu |
author_sort |
Naomichi Tanaka |
title |
Development of a High-Efficacy Reprogramming Method for Generating Human Induced Pluripotent Stem (iPS) Cells from Pathologic and Senescent Somatic Cells |
title_short |
Development of a High-Efficacy Reprogramming Method for Generating Human Induced Pluripotent Stem (iPS) Cells from Pathologic and Senescent Somatic Cells |
title_full |
Development of a High-Efficacy Reprogramming Method for Generating Human Induced Pluripotent Stem (iPS) Cells from Pathologic and Senescent Somatic Cells |
title_fullStr |
Development of a High-Efficacy Reprogramming Method for Generating Human Induced Pluripotent Stem (iPS) Cells from Pathologic and Senescent Somatic Cells |
title_full_unstemmed |
Development of a High-Efficacy Reprogramming Method for Generating Human Induced Pluripotent Stem (iPS) Cells from Pathologic and Senescent Somatic Cells |
title_sort |
development of a high-efficacy reprogramming method for generating human induced pluripotent stem (ips) cells from pathologic and senescent somatic cells |
publisher |
MDPI AG |
series |
International Journal of Molecular Sciences |
issn |
1661-6596 1422-0067 |
publishDate |
2020-09-01 |
description |
Induced pluripotent stem (iPS) cells are a type of artificial pluripotent stem cell induced by the epigenetic silencing of somatic cells by the Yamanaka factors. Advances in iPS cell reprogramming technology will allow aging or damaged cells to be replaced by a patient’s own rejuvenated cells. However, tissue that is senescent or pathologic has a relatively low reprogramming efficiency as compared with juvenile or robust tissue, resulting in incomplete reprogramming; iPS cells generated from such tissue types do not have sufficient differentiation ability and are therefore difficult to apply clinically. Here, we develop a new reprogramming method and examine it using myofibroblasts, which are pathologic somatic cells, from patient skin tissue and from each of the four heart chambers of a recipient heart in heart transplant surgery. By adjusting the type and amount of vectors containing transcriptional factors for iPS cell reprogramming, as well as adjusting the transfection load and culture medium, the efficiency of iPS cell induction from aged patient skin-derived fibroblasts was increased, and we successfully induced iPS cells from myocardial fibroblasts isolated from the pathologic heart of a heart transplant recipient. |
topic |
iPS cell myocardial fibroblast myofibroblast senescence pathologic state TGF-beta |
url |
https://www.mdpi.com/1422-0067/21/18/6764 |
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