Tumorigenicity assay essential for facilitating safety studies of hiPSC-derived cardiomyocytes for clinical application

Emiko Ito, Shigeru Miyagawa, Maki Takeda, Ai Kawamura, Akima Harada, Hiroko Iseoka, Shin Yajima, Nagako Sougawa, Noriko Mochizuki-Oda, Satoshi Yasuda, Yoji Sato, Yoshiki Sawa

Research output: Contribution to journalArticlepeer-review

12 Citations (Scopus)

Abstract

Transplantation of cardiomyocytes (CMs) derived from human induced pluripotent stem cells (hiPSC-CMs) is a promising treatment for heart failure, but residual undifferentiated hiPSCs and malignant transformed cells may lead to tumor formation. Here we describe a highly sensitive tumorigenicity assay for the detection of these cells in hiPSC-CMs. The soft agar colony formation assay and cell growth analysis were unable to detect malignantly transformed cells in hiPSC-CMs. There were no karyotypic abnormalities during hiPSCs subculture and differentiation. The hiPSC markers TRA1-60 and LIN28 showed the highest sensitivity for detecting undifferentiated hiPSCs among primary cardiomyocytes. Transplantation of hiPSC-CMs with a LIN28-positive fraction > 0.33% resulted in tumor formation in nude rats, whereas no tumors were formed when the fraction was < 0.1%. These findings suggested that combination of these in vitro and in vivo tumorigenecity assays can verify the safety of hiPSC-CMs for cell transplantation therapy.

Original languageEnglish
Article number1881
JournalScientific reports
Volume9
Issue number1
DOIs
Publication statusPublished - 2019 Dec 1
Externally publishedYes

ASJC Scopus subject areas

  • General

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