Future treatment of heart failure using human iPSC-derived cardiomyocytes

研究成果: Chapter

6 被引用数 (Scopus)

抄録

Heart transplantation can drastically improve survival in patients with a failing heart; however, the shortage of donor hearts remains a serious problem with this treatment strategy and the successful clinical application of regenerative medicine is eagerly awaited. To this end, we developed a novel method to generate human induced pluripotent stem cells (iPSCs) from circulating human T lymphocytes using Sendai virus containing Yamanaka factors. To establish an efficient cardiac differentiation protocol, we then screened factors expressed in the future heart site of early mouse embryos and identified several growth factors and cytokines that can induce cardiomyocyte differentiation and proliferation. Subsequent transcriptome and metabolome analysis on undifferentiated stem cells and cardiomyocytes to devise a specific metabolic environment for cardiomyocyte selection revealed completely different mechanisms of glucose and lactate metabolism. Based on these findings, we succeeded in metabolically selecting cardiomyocytes using glucose-free and lactate-supplemented medium, with up to 99 % purity and no teratoma formation. Using our aggregation technique, we also showed that >90 % of the transplanted cardiomyocytes survived in the heart and showed physiological growth after transplantation. We expect that combining these techniques will achieve future heart regeneration.

本文言語English
ホスト出版物のタイトルEtiology and Morphogenesis of Congenital Heart Disease
ホスト出版物のサブタイトルFrom Gene Function and Cellular Interaction to Morphology
出版社Springer Japan
ページ25-31
ページ数7
ISBN(電子版)9784431546283
ISBN(印刷版)9784431546276
DOI
出版ステータスPublished - 2016 1月 1

ASJC Scopus subject areas

  • 医学(全般)
  • 生化学、遺伝学、分子生物学(全般)

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