Distinct Metabolic Flow Enables Large-Scale Purification of Mouse and Human Pluripotent Stem Cell-Derived Cardiomyocytes
Distinct Metabolic Flow Enables Large-Scale Purification of Mouse and Human Pluripotent Stem Cell-Derived Cardiomyocytes
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DOI：
10.1016/j.stem.2012.09.013
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发表时间：
2013-01-03
期刊：
影响因子：
23.9
通讯作者：
Fukuda, Keiichi
中科院分区：
文献类型：
--
作者：
Tohyama, Shugo;Hattori, Fumiyuki;Fukuda, Keiichi
尽管医疗技术不断进步，心脏病仍然是死亡的主要原因。使用多能干细胞（PSC）的心脏再生疗法是心脏病患者的一种潜在的有前途的策略，但无法产生足够数量的高度纯化的心肌细胞一直是实现这一潜力的障碍。在这里，我们报告了一种非遗传方法，用于从小鼠和人PSC衍生物中大量生产心肌细胞，该方法基于心肌细胞和非心肌细胞（包括未分化细胞）之间葡萄糖和乳酸代谢的显著生化差异。我们用含有丰富乳酸的葡萄糖耗尽培养基培养PSC衍生物，发现只有心肌细胞存活。使用这种方法，我们获得了纯度高达99%的心肌细胞，这些细胞在移植后不会形成肿瘤。我们相信，我们的技术方法拓宽了纯化PSC衍生心肌细胞的潜在应用范围，并可能促进基于PSC的心脏再生治疗的进展。
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.