Distinct metabolic flow enables large-scale purification of mouse and human pluripotent stem cell-derived cardiomyocytes

Shugo Tohyama, Fumiyuki Hattori, Motoaki Sano, Takako Hishiki, Yoshiko Nagahata, Tomomi Matsuura, Hisayuki Hashimoto, Tomoyuki Suzuki, Hiromi Yamashita, Yusuke Satoh, Toru Egashira, Tomohisa Seki, Naoto Muraoka, Hiroyuki Yamakawa, Yasuyuki Ohgino, Tomofumi Tanaka, Masatoshi Yoichi, Shinsuke Yuasa, Mitsushige Murata, Makoto SuematsuKeiichi Fukuda

Research output: Contribution to journalArticlepeer-review

391 Citations (Scopus)

Abstract

Heart disease remains a major cause of death despite advances in medical technology. Heart-regenerative therapy that uses pluripotent stem cells (PSCs) is a potentially promising strategy for patients with heart disease, but the inability to generate highly purified cardiomyocytes in sufficient quantities has been a barrier to realizing this potential. Here, we report a nongenetic method for mass-producing cardiomyocytes from mouse and human PSC derivatives that is based on the marked biochemical differences in glucose and lactate metabolism between cardiomyocytes and noncardiomyocytes, including undifferentiated cells. We cultured PSC derivatives with glucose-depleted culture medium containing abundant lactate and found that only cardiomyocytes survived. Using this approach, we obtained cardiomyocytes of up to 99% purity that did not form tumors after transplantation. We believe that our technological method broadens the range of potential applications for purified PSC-derived cardiomyocytes and could facilitate progress toward PSC-based cardiac regenerative therapy.

Original languageEnglish
Pages (from-to)127-137
Number of pages11
JournalCell stem cell
Volume12
Issue number1
DOIs
Publication statusPublished - 2013 Jan 3

ASJC Scopus subject areas

  • Molecular Medicine
  • Genetics
  • Cell Biology

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