Molecular and phenotypic analyses of human embryonic stem cell-derived cardiomyocytes

Gareth Goh; Tim Self; Maria D. Barbadillo Muñoz; Ian P. Hall; Lorraine Young; Chris Denning

doi:10.1160/TH05-04-0268

Thrombosis and Haemostasis, Table of Contents

Thromb Haemost 2005; 94(04): 728-737
DOI: 10.1160/TH05-04-0268

Theme Issue Article

Schattauer GmbH

Molecular and phenotypic analyses of human embryonic stem cell-derived cardiomyocytes

Opportunities and challenges for clinical translation

Authors

Gareth Goh

¹Institute of Genetics, University of Nottingham, Queens Medical Centre, Nottingham, UK

²Division of Therapeutics and Molecular Medicine, University of Nottingham, Queens Medical Centre, Nottingham, UK
Tim Self

³Institute of Cell Signalling, University of Nottingham, Queens Medical Centre, Nottingham, UK
Maria D. Barbadillo Muñoz

¹Institute of Genetics, University of Nottingham, Queens Medical Centre, Nottingham, UK

⁴Division of Obstetrics and Gynaecology, University of Nottingham, Queens Medical Centre, Nottingham, UK
Ian P. Hall

²Division of Therapeutics and Molecular Medicine, University of Nottingham, Queens Medical Centre, Nottingham, UK
Lorraine Young

¹Institute of Genetics, University of Nottingham, Queens Medical Centre, Nottingham, UK

⁴Division of Obstetrics and Gynaecology, University of Nottingham, Queens Medical Centre, Nottingham, UK
Chris Denning

¹Institute of Genetics, University of Nottingham, Queens Medical Centre, Nottingham, UK

Abstract

Summary

Differentiation of human embryonic stem cells (hESCs) into cardiomyocytes in culture may offer unique opportunities for modeling genetic disorders, screening potentially cardiotoxic pharmaceutical agents or replacing cells of the diseased heart. However, before clinical utility can be realized, numerous hurdles must be overcome. Comprehensive molecular and phenotypic characterization is required but has so far been restricted to cardiomyocytes derived from a limited subset of hESC lines. Thus, we have initiated analysis of cardiomyocyte differentiation and function from a further two independently derived lines, BG01 and HUES-7. The challenge of improving cardiac cell induction, enrichment and maturation must also be addressed to meet the demands of high throughput pharmaceutical screening or to provide sufficient cells to repair an infarcted heart. Transplanted cells must functionally integrate without inducing arrhythmias, while survival and evasion of immune surveillance must be accomplished without tumorigenicity. This review evaluates the opportunities presented by hESC-derived cardiomyocytes and the progress towards surmounting the challenges of clinical translation.

Keywords

Human embryonic stem cells (hESC) - characterization - cardiomyocytes - differentiation - clinical translation

Full Text

References

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