Bone Marrow 3D Cell Constructs for Cardiac Tissue Repair

用于心脏组织修复的骨髓 3D 细胞构建体

• 批准号: 6833602
• 负责人: IKE W LEE
• 金额: $ 13.09万
• 依托单位: IVREA, INC.
• 依托单位国家: 美国
• 财政年份: 2004
• 资助国家: 美国
• 起止时间: 2004-09-15 至 2005-03-14
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6833602
• 关键词: angiogenesis; bioengineering /biomedical engineering; biomaterial compatibility; biomaterial development /preparation; bone marrow; cardiac myocytes; cardiogenesis; cardiovascular disorder therapy; cardiovascular transplantation; cell differentiation; cell growth regulation; cell proliferation; extracellular matrix; fibroblasts; growth factor; implant; laboratory rat; medical implant science; mesenchyme; myocardial infarction; nonhuman therapy evaluation; pluripotent stem cells; stem cell transplantation; tissue engineering; tissue support frame

DESCRIPTION (provided by applicant): Approximately 600,000 people die of cardiac cell death-related diseases such as coronary heart disease (CHD), acute myocardial infarct (AMI) and congestive heart failure (CHF). Current strategies for cardiac regeneration have generated a great deal of enthusiasm and stem cell technology in particular is been widely investigated as a potential new therapy for cell death-related heart diseases. Our objectives are to differentiate a large numbers of adult stem cells into committed cardiac lineages in vitro, and to further the technology to generate functional cardiac tissue including both cardiac myocytes and coronary microvasculature in vivo. To achieve this goal, we will grow bone marrow mesenchymal stem cells (BMSCs; Sca-1 and c-kit positive, CD34 negative cells), epicardial cells and cardiac fibroblasts, separately, in collagen-based biocompatible thread-like scaffolds. These cells will be ex vivo specified into cardiac lineages using growth factors, extra cellular matrix molecules, and intercellular interactions provided by 3-dimensional arrangements of the scaffolds. The most effective 3-D cellular construct will be transplanted into the myocardial infarcted area of a rat heart to test its survival, further differentiation and establishment of electromechanical connections to the neighboring host cardiac tissue. Our long-term goal is to develop autologous stem cell implants for MI patients.

描述（申请人提供）：大约 60 万人死于心肌细胞死亡相关疾病，如冠心病 (CHD)、急性心肌梗塞 (AMI) 和充血性心力衰竭 (CHF)。当前的心脏再生策略引起了极大的热情，特别是干细胞技术作为细胞死亡相关心脏病的潜在新疗法被广泛研究。我们的目标是在体外将大量成体干细胞分化为定向心脏谱系，并进一步发展在体内生成功能性心脏组织（包括心肌细胞和冠状动脉微脉管系统）的技术。为了实现这一目标，我们将在基于胶原蛋白的生物相容性线状支架中分别培养骨髓间充质干细胞（BMSC；Sca-1 和 c-kit 阳性细胞，CD34 阴性细胞）、心外膜细胞和心脏成纤维细胞。这些细胞将使用生长因子、细胞外基质分子以及支架的 3 维排列提供的细胞间相互作用在体外指定为心脏谱系。最有效的 3-D 细胞构建体将被移植到大鼠心脏的心肌梗塞区域，以测试其存活、进一步分化以及与邻近宿主心脏组织建立机电连接。我们的长期目标是为心肌梗死患者开发自体干细胞植入物。