Future treatment of heart failure using human iPSC-derived cardiomyocytes

Shugo Tohyama, Keiichi Fukuda

Research output: Chapter in Book/Report/Conference proceedingChapter

1 Citation (Scopus)

Abstract

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.

Original languageEnglish
Title of host publicationEtiology and Morphogenesis of Congenital Heart Disease: From Gene Function and Cellular Interaction to Morphology
PublisherSpringer Japan
Pages25-31
Number of pages7
ISBN (Electronic)9784431546283
ISBN (Print)9784431546276
DOIs
Publication statusPublished - 2016 Jan 1

Fingerprint

Induced Pluripotent Stem Cells
Stem cells
Treatment Failure
Cardiac Myocytes
Heart Failure
Lactic Acid
Sendai virus
Glucose
Regenerative Medicine
Metabolome
Teratoma
Gene Expression Profiling
Heart Transplantation
T-cells
Regeneration
Intercellular Signaling Peptides and Proteins
Viruses
Metabolism
Stem Cells
Embryonic Structures

Keywords

  • Cardiomyocyte
  • Human
  • Induced pluripotent stem cell
  • Purification
  • Transplantation

ASJC Scopus subject areas

  • Medicine(all)
  • Biochemistry, Genetics and Molecular Biology(all)

Cite this

Tohyama, S., & Fukuda, K. (2016). Future treatment of heart failure using human iPSC-derived cardiomyocytes. In Etiology and Morphogenesis of Congenital Heart Disease: From Gene Function and Cellular Interaction to Morphology (pp. 25-31). Springer Japan. https://doi.org/10.1007/978-4-431-54628-3_4

Future treatment of heart failure using human iPSC-derived cardiomyocytes. / Tohyama, Shugo; Fukuda, Keiichi.

Etiology and Morphogenesis of Congenital Heart Disease: From Gene Function and Cellular Interaction to Morphology. Springer Japan, 2016. p. 25-31.

Research output: Chapter in Book/Report/Conference proceedingChapter

Tohyama, S & Fukuda, K 2016, Future treatment of heart failure using human iPSC-derived cardiomyocytes. in Etiology and Morphogenesis of Congenital Heart Disease: From Gene Function and Cellular Interaction to Morphology. Springer Japan, pp. 25-31. https://doi.org/10.1007/978-4-431-54628-3_4
Tohyama S, Fukuda K. Future treatment of heart failure using human iPSC-derived cardiomyocytes. In Etiology and Morphogenesis of Congenital Heart Disease: From Gene Function and Cellular Interaction to Morphology. Springer Japan. 2016. p. 25-31 https://doi.org/10.1007/978-4-431-54628-3_4
Tohyama, Shugo ; Fukuda, Keiichi. / Future treatment of heart failure using human iPSC-derived cardiomyocytes. Etiology and Morphogenesis of Congenital Heart Disease: From Gene Function and Cellular Interaction to Morphology. Springer Japan, 2016. pp. 25-31
@inbook{99251c3703eb44db9a20ba19d4197cdd,
title = "Future treatment of heart failure using human iPSC-derived cardiomyocytes",
abstract = "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.",
keywords = "Cardiomyocyte, Human, Induced pluripotent stem cell, Purification, Transplantation",
author = "Shugo Tohyama and Keiichi Fukuda",
year = "2016",
month = "1",
day = "1",
doi = "10.1007/978-4-431-54628-3_4",
language = "English",
isbn = "9784431546276",
pages = "25--31",
booktitle = "Etiology and Morphogenesis of Congenital Heart Disease: From Gene Function and Cellular Interaction to Morphology",
publisher = "Springer Japan",

}

TY - CHAP

T1 - Future treatment of heart failure using human iPSC-derived cardiomyocytes

AU - Tohyama, Shugo

AU - Fukuda, Keiichi

PY - 2016/1/1

Y1 - 2016/1/1

N2 - 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.

AB - 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.

KW - Cardiomyocyte

KW - Human

KW - Induced pluripotent stem cell

KW - Purification

KW - Transplantation

UR - http://www.scopus.com/inward/record.url?scp=85006760608&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85006760608&partnerID=8YFLogxK

U2 - 10.1007/978-4-431-54628-3_4

DO - 10.1007/978-4-431-54628-3_4

M3 - Chapter

AN - SCOPUS:85006760608

SN - 9784431546276

SP - 25

EP - 31

BT - Etiology and Morphogenesis of Congenital Heart Disease: From Gene Function and Cellular Interaction to Morphology

PB - Springer Japan

ER -