MOLECULAR AND CELLULAR BIOLOGY OF CARDIAC INTERSTITIUM

心脏间质的分子和细胞生物学

• 批准号: 3362246
• 负责人: DONALD STAVE KOHTZ
• 金额: $ 8.69万
• 依托单位: MOUNT SINAI SCHOOL OF MEDICINE OF CUNY
• 依托单位国家: 美国
• 财政年份: 1989
• 资助国家: 美国
• 起止时间: 1989-07-01 至 1994-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3362246
• 关键词: cell differentiation; cell growth regulation; collagen; embryo /fetus culture; endocardium; endoderm; extracellular matrix; gene expression; heart cell; histogenesis; human fetus tissue; human tissue; immunofluorescence technique; laboratory mouse; mammalian embryology; mixed tissue /cell culture; myoblasts; myocardium; myogenesis; pericardium; tissue /cell culture

Proliferating cardiac myoblasts are observed in situ only during a short developmental period in early embryogenesis, after which all of the muscle cells of the myocardium - even the proliferating cells - bear contractile elements and are partially differentiated. Since the partially differentiated cells possess only a limited capacity for mitotic growth, replication of cardiac myocytes stops soon after birth, leaving the myocardium with no significant regenerative ability. The components of the embryonic extracellular matrix in which cardiac myoblasts proliferate and differentiate are quite different from those of fetal or adult heart, and their composition and architecture are not well understood. One reason is the limited amount of material available for analysis at such an early developmental period. To fully understand the induction of cardiac myogenesis, a better understanding of the cellular and extracellular matrix components of the embryonic heart is required. The purpose of this proposal is to recreate in culture the earliest events of cardiac organogenesis observed in the embryo. Based on in situ observations, such culture systems should consist of three cellular components: cardiac myoblasts, endodermal cells, and embryonic endocardial cells. The extracellular matrix components should include the basal lamina between the endoderm and the cardiac myoblast and cardiac jelly found between the embryonic endocardium and the cardiac myoblasts. In this proposal, culture equivalents for all three cellular components will be characterized. Co- culture experiments are proposed that will examine the inductive interactions between these three embryonic cell types, and the mechanisms that lead to the elaboration of the embryonic cardiac matrices. Defined embryonic, fetal and adult extracellular matrices then will be assembled in vitro, and their effects on the phenotypes of cardiac myoblasts and myocytes will be elucidated. By comparing the cellular and extracellular components of the embryonic and adult heart, insights should be gained into the forces that stifle regeneration of the myocardium.

仅在原位观察到增生的心脏肌细胞 早期胚胎发生的短发期，之后 心肌的所有肌肉细胞 - 甚至增殖 细胞 - 带收缩元件，部分分化。 由于部分分化的细胞仅具有有限的 有丝分裂生长的能力，心肌细胞的复制 出生后不久，离开心肌没有明显的 再生能力。 胚胎的成分 心脏肌细胞增生和的细胞外基质 区分与胎儿或成人完全不同 心脏及其组成和建筑不好 理解。 原因之一是可用的材料数量有限 在这样的早期发育时期进行分析。 完全 了解心脏肌发生的诱导，更好 了解细胞和细胞外基质成分 需要胚胎心脏。 该提议的目的 是在文化中重现心脏的最早事件 在胚胎中观察到的器官发生。 基于原位 观察结果，这种培养系统应由三个细胞组成 成分：心脏肌细胞，内皮细胞和胚胎 心内膜细胞。 细胞外基质组件应 包括内胚层和心脏之间的基底层 在胚胎心内膜外发现了肌细胞和心脏果冻 和心脏肌细胞。 在这个建议中，文化等效物 对于所有三个细胞组件，都将表征。 共同 提出了将检查归纳的培养实验 这三种胚胎细胞类型与 导致胚胎心脏阐述的机制 矩阵。 定义的胚胎，胎儿和成人细胞外 然后，矩阵将在体外组装，它们对 心脏肌细胞和心肌细胞的表型将被阐明。 通过比较细胞和细胞外成分 胚胎和成人心脏，应获得见解 扼杀心肌再生的力。