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

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.

人类胚胎干细胞（human embryonic stem cells, hESCs）可作为近乎无限的细胞来源，有望实现病变组织与器官的再生修复。本研究探讨了人类胚胎干细胞衍生心肌细胞（human embryonic stem cell-derived cardiomyocytes, hESC-CMs）在小鼠模型中促进心脏缺血再灌注损伤修复的应用效果。本研究借助基因芯片（microarrays）技术，解析了未分化人类胚胎干细胞与胎儿心肌细胞之间的分化变化谱系，并明确了hESC-CMs的转录组（transcriptome）特征。结果显示，hESC-CMs的心肌细胞基因表达水平与20周胎龄的胎儿心肌细胞相近，表明该细胞群体是体内潜在的优质替代细胞来源。超声心动图（echocardiography）检测结果表明，移植后8周小鼠心脏功能得到显著改善。最后，本研究通过分子成像（molecular imaging）技术在体内追踪细胞的定位、存活与增殖情况，证实了hESC-CMs可长期定植于体内。综上，对人类胚胎干细胞分化过程的全局基因表达谱分析，可实现对驱动胚胎干细胞命运决定的生物学过程、调控网络及关键基因的系统级解析；此类研究将为干细胞疗法未来的临床应用奠定重要基础。