Molecular and phenotypic analyses of human embryonic stem cell-derived cardiomyocytes: opportunities and challenges for clinical translation.
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.
Goh
Gareth
G
Institute of Genetics, University of Nottingham, Queens Medical Centre, Nottingham, UK.
Self
Tim
T
Barbadillo Muñoz
Maria D
MD
Hall
Ian P
IP
Young
Lorraine
L
Denning
Chris
C
D002454:Cell Differentiation / Q000502:physiology; D006331:Heart Diseases / Q000628:therapy*; D006801:Humans; D032383:Myocytes, Cardiac / Q000166:cytology / Q000502:physiology*; D010641:Phenotype; D033581:Stem Cell Transplantation; D013234:Stem Cells / Q000166:cytology / Q000502:physiology*; D014158:Transcription, Genetic / Q000502:physiology