Distinct Metabolic Flow Enables Large-Scale Purification of Mouse and Human Pluripotent Stem Cell-Derived Cardiomyocytes

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• 作者：Shugo Tohyama¹ ; ³ ; Fumiyuki Hattori¹ ; ⁴ ; ^{hattori.fumiyuki.ef@asubio.co.jp} ; Motoaki Sano¹ ; Takako Hishiki² ; Yoshiko Nagahata² ; ⁵ ; Tomomi Matsuura² ; ⁵ ; Hisayuki Hashimoto¹ ; Tomoyuki Suzuki⁶ ; Hiromi Yamashita¹ ; ⁴ ; Yusuke Satoh¹ ; Toru Egashira¹ ; Tomohisa Seki¹ ; Naoto Muraoka¹ ; Hiroyuki Yamakawa¹ ; Yasuyuki Ohgino¹ ; Tomofumi Tanaka⁴ ; Masatoshi Yoichi⁴ ; Shinsuke Yuasa¹ ; Mitsushige Murata¹ ; Makoto Suematsu² ; ⁵ ; Keiichi Fukuda¹ ; ^{kfukuda@a2.keio.jp}
• 刊名：Cell Stem Cell
• 出版年：2013
• 出版时间：3 January, 2013
• 年：2013
• 卷：12
• 期：1
• 页码：127-137
• 全文大小：2421 K

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Summary

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.