title: Distinct metabolic flow enables large-scale purification of mouse and human pluripotent stem cell-derived cardiomyocytes.
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.
authors.affiliation: Department of Cardiology, Keio University School of Medicine, Tokyo, Japan.
authors.forename: Shugo
authors.initials: S
authors.lastname: Tohyama
authors.forename: Fumiyuki
authors.initials: F
authors.lastname: Hattori
authors.forename: Motoaki
authors.initials: M
authors.lastname: Sano
authors.forename: Takako
authors.initials: T
authors.lastname: Hishiki
authors.forename: Yoshiko
authors.initials: Y
authors.lastname: Nagahata
authors.forename: Tomomi
authors.initials: T
authors.lastname: Matsuura
authors.forename: Hisayuki
authors.initials: H
authors.lastname: Hashimoto
authors.forename: Tomoyuki
authors.initials: T
authors.lastname: Suzuki
authors.forename: Hiromi
authors.initials: H
authors.lastname: Yamashita
authors.forename: Yusuke
authors.initials: Y
authors.lastname: Satoh
authors.forename: Toru
authors.initials: T
authors.lastname: Egashira
authors.forename: Tomohisa
authors.initials: T
authors.lastname: Seki
authors.forename: Naoto
authors.initials: N
authors.lastname: Muraoka
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Yamakawa
authors.forename: Yasuyuki
authors.initials: Y
authors.lastname: Ohgino
authors.forename: Tomofumi
authors.initials: T
authors.lastname: Tanaka
authors.forename: Masatoshi
authors.initials: M
authors.lastname: Yoichi
authors.forename: Shinsuke
authors.initials: S
authors.lastname: Yuasa
authors.forename: Mitsushige
authors.initials: M
authors.lastname: Murata
authors.forename: Makoto
authors.initials: M
authors.lastname: Suematsu
authors.forename: Keiichi
authors.initials: K
authors.lastname: Fukuda
mesh_terms: D000818:Animals; D018929:Cell Culture Techniques / Q000379:methods*; D006801:Humans; D051379:Mice; D032383:Myocytes, Cardiac / Q000166:cytology*; D039904:Pluripotent Stem Cells / Q000166:cytology*