Transcriptional and functional profiling of human embryonic stem cell-derived cardiomyocytes

• Published in: PloS one 2008-10, Vol.3 (10), p.e3474
• Main Authors: Cao, Feng, Wagner, Roger A, Wilson, Kitchener D, Xie, Xiaoyan, Fu, Ji-Dong, Drukker, Micha, Lee, Andrew, Li, Ronald A, Gambhir, Sanjiv S, Weissman, Irving L, Robbins, Robert C, Wu, Joseph C
• Format: Article
• Language: English
• Subjects: Animals; Bioengineering; Biological activity; Cardiology; Cardiomyocytes; Cardiovascular Disorders/Cardiovascular Imaging; Cardiovascular Disorders/Coronary Artery Disease; Cardiovascular Disorders/Heart Failure; Cell Biology/Gene Expression; Cell Differentiation; Cell survival; Clinical trials; Developmental biology; Developmental Biology/Cell Differentiation; Developmental Biology/Stem Cells; DNA microarrays; Drosophila; Electrocardiography; Embryo cells; Embryonic stem cells; Embryonic Stem Cells - cytology; Embryonic Stem Cells - transplantation; Engraftment; Fetuses; Gene expression; Gene Expression Profiling; Genes; Genetic aspects; Genetic research; Genetics and Genomics/Bioinformatics; Genetics and Genomics/Gene Expression; Genomics; Graft Survival; Heart; Heart cells; Heart diseases; Heart failure; Heart function; Humans; In vivo methods and tests; Insects; Ischemia; Localization; Mice; MicroRNAs; Models, Animal; Myocardial Reperfusion Injury - therapy; Myocytes, Cardiac - cytology; Myocytes, Cardiac - transplantation; Nuclear medicine; Oligonucleotide Array Sequence Analysis; Organs; Regeneration; Reperfusion; Stem cell transplantation; Stem Cell Transplantation - methods; Stem cells; Therapeutic applications; Transcription; Transcription (Genetics); Transcription, Genetic; Transplantation; Transplantation, Heterologous; Treatment Outcome
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0003474

Human embryonic stem cells (hESCs) can serve as a potentially limitless source of cells that may enable regeneration of diseased tissue and organs. Here we investigate the use of human embryonic stem cell-derived cardiomyocytes (hESC-CMs) in promoting recovery from cardiac ischemia reperfusion injury in a mouse model. Using microarrays, we have described the hESC-CM transcriptome within the spectrum of changes that occur between undifferentiated hESCs and fetal heart cells. The hESC-CMs expressed cardiomyocyte genes at levels similar to those found in 20-week fetal heart cells, making this population a good source of potential replacement cells in vivo. Echocardiographic studies showed significant improvement in heart function by 8 weeks after transplantation. Finally, we demonstrate long-term engraftment of hESC-CMs by using molecular imaging to track cellular localization, survival, and proliferation in vivo. Taken together, global gene expression profiling of hESC differentiation enables a systems-based analysis of the biological processes, networks, and genes that drive hESC fate decisions, and studies such as this will serve as the foundation for future clinical applications of stem cell therapies.