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）：当内皮细胞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血管系统结合。虽然该系统具有很大的临床应用潜力，但它还不够强大。其主要原因是移植细胞无法通过吻合与宿主血管连接，目前对这一过程的了解甚少。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。血管吻合的机制包括移植细胞对血管的包裹、宿主血管壁的破坏和内皮连接的重新分配。这一过程允许新生血管“接入”已有的血管网络。拟议的项目将通过专门针对阻碍攻丝的成分加速这一过程，包括基膜（Aim 1）、宿主周细胞（Aim 2）和宿主内皮（Aim 3）。