Transcriptional and Functional Profiling of Human Embryonic Stem Cell-Derived Cardiomyocytes

Abstract

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.

Determination of the Human Cardiomyocyte mRNA and miRNA Differentiation Network by Fine-Scale Profiling

“…2A; R 2 = 0.64 day 28 vs. fetal heart; R 2 = 0.69 day 120 vs. fetal heart). The strong correlation between fetal heart and the iPS-derived cardiomyocytes was expected and has been observed in other examinations of pluripotent stem cells differentiating toward cardiomyocytes [16,34]. Once the cardiomyocyte population had been established, the R 2 values continued to rise in a linear fashion when compared with the adult tissues (R 2 = 0.55 day 28 vs. total 1; R 2 = 0.65 day 120 vs. total 1).…”

Global DNA methylation and transcriptional analyses of human ESC-derived cardiomyocytes

“…Recent efforts have successfully developed several protocols, by which hESCs can be differentiated into hCMs (Yang et al, 2008;Kattman et al, 2011;Lian et al, 2012;Willems et al, 2012;Zhang et al, 2012). Furthermore, hESC-derived hCMs have been analyzed by microarray and a group of cardiospecific genes were revealed (Beqqali et al, 2006;Cao et al, 2008;Synnergren et al, 2008). However, one inevitable concern is that by these published differentiation protocols, it is difficult to obtain pure hCMs.…”

Differentiation of Human Atrial Myocytes From Endothelial Progenitor Cell-Derived Induced Pluripotent Stem Cells

“…An alternative method for cardiac differentiation is based on the role endoderm cells play to provide signals to adjacent mesoderm cell for during embryonic development [227][228][229][230]. Visceral endoderm like cells (END2), which derive from mouse P19 embryonal carcinoma, have been designed for cardiac induction.…”

“…Cardiac differentiation from pluripotent stem cells can be derived by guided differentiation in adherent culture involving serum free medium supplemented with growth factors Activin A and BMP4 [55,[221][222][223][224][225][226][227][228][229][230][231][232][233][234][235][236][237][238][239]. These growth factors are a member of the TGF b family that plays roles in embryonic development including induction of gastrulation-like events, meso-endoderm development and induction of cardiogenesis [240][241][242][243][244][245][246].…”