Development of a high-efficacy reprogramming method for generating human induced pluripotent stem (Ips) cells from pathologic and senescent somatic cells

Naomichi Tanaka, Hidemasa Kato, Hiromi Tsuda, Yasunori Sato, Toshihiro Muramatsu, Atsushi Iguchi, Hiroyuki Nakajima, Akihiro Yoshitake, Takaaki Senbonmatsu

Research output: Contribution to journalArticlepeer-review

Abstract

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.

Original languageEnglish
Article number6764
Pages (from-to)1-16
Number of pages16
JournalInternational journal of molecular sciences
Volume21
Issue number18
DOIs
Publication statusPublished - 2020 Sep 2

Keywords

  • IPS cell
  • Myocardial fibroblast
  • Myofibroblast
  • Pathologic state
  • Senescence
  • TGF-beta

ASJC Scopus subject areas

  • Catalysis
  • Molecular Biology
  • Spectroscopy
  • Computer Science Applications
  • Physical and Theoretical Chemistry
  • Organic Chemistry
  • Inorganic Chemistry

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