Encouraging anastomosis of engrafted vascular networks

促进移植血管网络的吻合

• 批准号: 8440749
• 负责人: LANCE L MUNN
• 金额: $ 32.91万
• 依托单位: MASSACHUSETTS GENERAL HOSPITAL
• 依托单位国家: 美国
• 财政年份: 2012
• 资助国家: 美国
• 起止时间: 2012-03-08 至 2016-02-28
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8440749
• 关键词: Anastomosis - action; Angiopoietin-2; Antibodies; Basement membrane; Binding; Blood; Blood Vessels; Blood flow; Cells; DC101 Monoclonal Antibody; Dissociation; Endothelial Cells; Endothelium; Engineering; Failure; Gel; Gelatinase B; Imatinib; Implant; Knowledge; Matrix Metalloproteinases; Membrane; Metalloproteases; Perfusion; Pericytes; Process; Production; Recombinant Proteins; Signal Transduction; System; TNF gene; Theft; Tissue Engineering; Transforming Growth Factors; Transplanted tissue; Vascular Endothelial Growth Factor Receptor-2; Vascular Endothelial Growth Factors; Work; animal tissue; antileukoprotease; cadherin 5; clinical application; follow-up; human SLPI protein; intravital imaging; mouse model; overexpression

DESCRIPTION (provided by applicant): When embedded in collagenous gel and implanted into animal tissue, endothelial cells can form networks and integrate with the host vasculature. Although this system has great potential for clinical applications, it is not yet sufficiently robust. A major reason for this is failure of the engrafted cells to connect with the host blood vessels through anastomosis, and very little is known about this process. Using longitudinal intravital imaging, we identified the mechanism responsible for the connections, and determined the rate-limiting step that slows the perfusion. The mechanism of vessel anastomosis involves wrapping of existing vessels by the engrafted cells, disruption of the host vessel wall and endothelial junction reassignment. The process allows the nascent vessels to "tap" into the pre-existing network. The proposed project will accelerate this process by specifically targeting components that hinder tapping, including basement membrane (Aim 1), host pericytes (Aim 2) and host endothelium (Aim 3).

描述（由申请人提供）：当嵌入胶原凝胶并植入动物组织时，内皮细胞可以形成网络并与宿主脉管系统整合。尽管该系统具有巨大的临床应用潜力，但还不够稳健。造成这种情况的一个主要原因是移植细胞未能通过吻合术与宿主血管连接，而人们对这一过程知之甚少。使用纵向活体成像，我们确定了负责连接的机制，并确定了减慢灌注的限速步骤。血管吻合的机制涉及移植细胞包裹现有血管、破坏宿主血管壁和内皮连接重新分配。该过程允许新生血管“接入”预先存在的网络。拟议的项目将通过专门针对阻碍敲击的成分来加速这一过程，包括基底膜（目标 1）、宿主周细胞（目标 2）和宿主内皮细胞（目标 3）。