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首页> 外文期刊>Journal of tissue engineering and regenerative medicine >Generation of clinical-grade functional cardiomyocytes from human embryonic stem cells in chemically defined conditions
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Generation of clinical-grade functional cardiomyocytes from human embryonic stem cells in chemically defined conditions

机译：从化学定义的病症中从人胚胎干细胞产生临床级功能性心肌细胞

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摘要

A highly efficient cardiac differentiation from human pluripotent stem cells (hPSCs) is achievable using existing methods, especially with the standard B27 induction system. However, bovine serum albumin (BSA), one of the essential ingredients in B27, may pose significant complications for clinical studies owing to its animal origin and potential risks of virus contamination. Furthermore, the high cost of the B27 induction system also limits the applications of hPSCs-derived cardiomyocytes. Here, a BSA-free and chemically defined medium has been developed for differentiating hPSCs to clinical-grade cardiomyocytes, which generated over 80% cardiac troponin T (cTNT)-positive cardiomyocytes with high yield. When engrafting the cardiomyocytes into the hearts of myocardial infarction model rats, the rats survived with significantly improved heart functions in ejection fraction and fractional shortening. Importantly, the human embryonic stem cell (hESC) line (Q-CTS-hESC-2) chosen for differentiation was of a clinical-grade maintained in defined xeno-free conditions. Compliant with the biological safety requirements, the Q-CTS-hESC-2-derived cardiomyocytes have passed the sterility and pathogen criteria tests for clinical applications. This study reports, for the first time, the generation of clinical-grade and functional cardiomyocytes from hPSCs where BSA-free and chemically defined conditions were maintained throughout the whole process. This provides the possibility of future therapeutic use of clinical-grade hPSCs-derived cardiomyocytes in treating heart diseases. Copyright (C) 2016 John Wiley & Sons, Ltd.
机译：使用现有方法可以实现从人多能干细胞（HPSC）的高效心脏分化，尤其是标准B27诱导系统。然而，牛血清白蛋白（BSA）是B27的必要成分之一，由于其动物来源和病毒污染的潜在风险，可能会对临床研究产生显着的并发症。此外，B27诱导系统的高成本也限制了HPSCS衍生的心肌细胞的应用。这里，已经开发了一种无BSA和化学定义的培养基，用于将HPSCS分化为临床级心肌细胞，其产生超过80％的心肌肌钙蛋白T（CTNT） - 阳性心肌细胞，高产率。当对心肌细胞的心脏缩合到心肌梗死模型大鼠的心脏时，大鼠在喷射分数和分数缩短中具有显着改善的心脏功能。重要的是，选择用于分化的人胚胎干细胞（HESC）线（Q-CTS-HESC-2）是在定义的无异卵条件下保持的临床级。符合生物安全要求，Q-CTS-HESC-2衍生的心肌细胞通过无菌和病原体标准测试对临床应用。本研究报告称，首次从HPSC中产生临床级和功能性心肌细胞，其中在整个过程中保持无BSA和化学定义的条件。这提供了未来治疗级HPSCS衍生的心肌细胞治疗心脏病的可能性。版权所有（c）2016 John Wiley＆Sons，Ltd。

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  • 作者

    Tan Yuanqing; Han Pengcheng; Gu Qi; Chen Gang; Wang Lei; Ma Ruoyu; Wu Jun; Feng Chunjing; Zhang Ying; Wang Liu; Hu Baoyang; Li Wei; Hao Jie; Zhou Qi;

  • 作者单位

    Chinese Acad Sci Inst Zool State Key Lab Stem Cell &

    Reprod Biol Beijing 100101 Peoples R China;

    Chinese Acad Sci Inst Zool State Key Lab Stem Cell &

    Reprod Biol Beijing 100101 Peoples R China;

    Chinese Acad Sci Inst Zool State Key Lab Stem Cell &

    Reprod Biol Beijing 100101 Peoples R China;

    Chinese Acad Sci Inst Zool State Key Lab Stem Cell &

    Reprod Biol Beijing 100101 Peoples R China;

    Chinese Acad Sci Inst Zool State Key Lab Stem Cell &

    Reprod Biol Beijing 100101 Peoples R China;

    Chinese Acad Sci Inst Zool State Key Lab Stem Cell &

    Reprod Biol Beijing 100101 Peoples R China;

    Chinese Acad Sci Inst Zool State Key Lab Stem Cell &

    Reprod Biol Beijing 100101 Peoples R China;

    Chinese Acad Sci Inst Zool State Key Lab Stem Cell &

    Reprod Biol Beijing 100101 Peoples R China;

    Chinese Acad Sci Inst Zool State Key Lab Stem Cell &

    Reprod Biol Beijing 100101 Peoples R China;

    Chinese Acad Sci Inst Zool State Key Lab Stem Cell &

    Reprod Biol Beijing 100101 Peoples R China;

    Chinese Acad Sci Inst Zool State Key Lab Stem Cell &

    Reprod Biol Beijing 100101 Peoples R China;

    Chinese Acad Sci Inst Zool State Key Lab Stem Cell &

    Reprod Biol Beijing 100101 Peoples R China;

    Chinese Acad Sci Inst Zool State Key Lab Stem Cell &

    Reprod Biol Beijing 100101 Peoples R China;

    Chinese Acad Sci Inst Zool State Key Lab Stem Cell &

    Reprod Biol Beijing 100101 Peoples R China;

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  • 原文格式 PDF
  • 正文语种 eng
  • 中图分类 基础医学;
  • 关键词

    chemically defined; cardiomyocytes; human pluripotent stem cells; biological safety; clinical-grade;

    机译：化学定义;心肌细胞;人多能干细胞;生物安全;临床等级;

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