Control of Stem Cell Fate in Heart Coculture

描述（由申请人提供）：心血管疾病是美国最令人衰弱的疾病之一。 目前，导致发育异常或患病心脏修复的机制尚不清楚。 移植研究中令人鼓舞的结果已经显示了心脏细胞替代。 然而，目前还不知道哪种细胞类型或微环境对细胞替代最有效。 该提案将检查人胚胎干细胞（hES）、NIH登记号WA 01和胚胎生殖细胞（hEG）修复或重建发育异常或受损心脏模型的能力。 在目标1中，器官共培养将用于在胚胎第7-12天的小鼠心脏中创造类似于体内的心肌细胞分化的环境。 目的2将检查人类ES或EG细胞在Gja 1基因突变的小鼠（具有先天性心脏畸形）中重新填充心脏干细胞龛的能力，以及修复白喉毒素损伤的心脏组织的能力，以确定心脏干细胞龛在指导hEG或hES分化中的作用。 在目的3中，心脏神经嵴细胞与hES或hEG细胞的共培养将用于确定这些细胞是否也能够指导心肌细胞分化。

DESCRIPTION (provided by applicant): Cardiovascular disease is one of the most debilitating diseases in America. Currently, mechanisms leading to repair of developmentally abnormal or diseased hearts is unknown. Encouraging results in transplantation studies have been shown with cardiac cell replacement. However, it is not known which cell types or microenvironment will be the most efficient for cell replacement. This proposal will examine the ability of human embryonic stem (hES), NIH registry no. WA01, and embryonic germ cells (hEG) for repair or repopulation of developmentally abnormal or damaged heart models. In Aim 1, organ coculture will be used to create an environment similar to in vivo for differentiation of cardiomyocytes in embryonic day 7-12 mouse hearts. Aim 2 will examine the ability of human ES or EG cells to repopulate the cardiac stem cell niche in mice with a mutation in the Gja1 gene, which have congenital cardiac abnormalities, and also to repair heart tissue damaged by diptheria toxin to determine the role of the cardiac stem cell niche in directing hEG or hES differentiation. In Aim 3, coculture of cardiac neural crest cells with hES or hEG cells will be used to determine if these cells may also be able to direct cardiomyocyte differentiaton.