TY - JOUR
T1 - Development of a high-efficacy reprogramming method for generating human induced pluripotent stem (Ips) cells from pathologic and senescent somatic cells
AU - Tanaka, Naomichi
AU - Kato, Hidemasa
AU - Tsuda, Hiromi
AU - Sato, Yasunori
AU - Muramatsu, Toshihiro
AU - Iguchi, Atsushi
AU - Nakajima, Hiroyuki
AU - Yoshitake, Akihiro
AU - Senbonmatsu, Takaaki
N1 - Funding Information:
Funding: This study was funded by a KAKENHI Grant-in Aid for Scientific Research (B) 26293313 to T.S., and the Saitama Medical University Maruki Memorial Foundation, Novartis Foundation, MSD Foundation, and Otsuka Foundation.
Funding Information:
This study was funded by a KAKENHI Grant-in Aid for Scientific Research (B) 26293313 to T.S., and the Saitama Medical University Maruki Memorial Foundation, Novartis Foundation, MSD Foundation, and Otsuka Foundation.
Publisher Copyright:
© 2020 by the authors. Licensee MDPI, Basel, Switzerland.
PY - 2020/9/2
Y1 - 2020/9/2
N2 - 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.
AB - 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.
KW - IPS cell
KW - Myocardial fibroblast
KW - Myofibroblast
KW - Pathologic state
KW - Senescence
KW - TGF-beta
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U2 - 10.3390/ijms21186764
DO - 10.3390/ijms21186764
M3 - Article
C2 - 32942642
AN - SCOPUS:85090886745
VL - 21
SP - 1
EP - 16
JO - International Journal of Molecular Sciences
JF - International Journal of Molecular Sciences
SN - 1661-6596
IS - 18
M1 - 6764
ER -