Vascularization of engineered cardiac tissue

工程心脏组织的血管化

• 批准号: 7371992
• 负责人: ROBERT Samuel LANGER
• 金额: $ 33.55万
• 依托单位: MASSACHUSETTS INSTITUTE OF TECHNOLOGY
• 依托单位国家: 美国
• 财政年份: 1998
• 资助国家: 美国
• 起止时间: 1998-07-10 至 2009-02-28
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7371992
• 关键词: Address; Adhesions; Amino Acids; Anastomosis - action; Animal Model; Antibodies; Applications Grants; Bioreactors; Biotechnology; Blood; Blood Vessels; Cardiac; Cardiac Myocytes; Cardiovascular system; Cell Differentiation process; Cell Survival; Cell-Matrix Junction; Cells; Coculture Techniques; Complex; Condition; Cultured Cells; Devices; Embryo; Endothelial Cells; Engineering; Extracellular Matrix; Film; Goals; Growth; Heart; Human; Immunodeficient Mouse; Implant; In Vitro; Journals; Liver; Mechanics; Mesenchymal; Modification; Monitor; Nature; Paper; Peptides; Polymers; Process; Property; Publishing; Rattus; Research; Science; Seeds; Shapes; Signal Transduction; Site; Stem cells; Structure; Surface; System; Testing; Thick; Time; Tissue Engineering; Tissues; Tube; Umbilical vein; Vascular Endothelial Growth Factors; Vascularization; adhesion receptor; angiogenesis; base; biodegradable polymer; cell assembly; cell type; design; desire; embryonic stem cell; human embryonic stem cell; human tissue; implantation; in vivo; neovascularization; novel; progenitor; scaffold; stem; subcutaneous; vasculogenesis

DESCRIPTION (provided by applicant): 1 of the major obstacles in tissue engineering of thick, complex tissues (such as the heart and the liver) is the need to vascularize the tissue in vitro. Vascularization in vitro could restore cells viability during growth of the tissue, induce structural organization and promote integration upon implantation. Embryonic stem (ES) cells have the capability to differentiate and form blood vessels de novo in a process called vasculogenesis. We have shown that human ES (hES) cells can differentiate into endothelial cells (ECs) forming vascular-like structures when formation of embryoid bodies is induced and that these cells can be isolated and grown in culture. We hypothesize that the vasculogenic potential of hES-derived endothelial progenitors can be used to induce vascularization in engineered human tissue. Our goal will be to induce vasculogenesis in engineered tissue constructs grown on three dimensional (3D) polymer scaffolds. We will use co culture systems of embryonic endothelial and cardiac cells cultured on biodegradable polymer scaffolds designed to meet cellular and mechanical properties needed for a cardiac patch. The vascularized constructs will be implanted and examined for integration with the host vasculature. We hypothesize that the vessel network created in vitro will promote the vascularization of the tissue in vivo.

描述（由申请人提供）：厚而复杂的组织（例如心脏和肝脏）的组织工程的主要障碍之一是需要在体外​​使组织血管化。体外血管化可以恢复组织生长过程中的细胞活力，诱导结构组织并促进植入后的整合。胚胎干 (ES) 细胞具有在称为血管发生的过程中从头分化和形成血管的能力。我们已经证明，当诱导胚状体形成时，人 ES (hES) 细胞可以分化为形成血管样结构的内皮细胞 (EC)，并且可以分离这些细胞并在培养物中生长。我们假设 hES 衍生的内皮祖细胞的血管生成潜力可用于诱导工程人体组织中的血管化。我们的目标是在三维（3D）聚合物支架上生长的工程组织结构中诱导血管生成。我们将使用在可生物降解的聚合物支架上培养的胚胎内皮细胞和心脏细胞的共培养系统，旨在满足心脏补片所需的细胞和机械性能。血管化构建体将被植入并检查与宿主脉管系统的整合。我们假设体外创建的血管网络将促进体内组织的血管化。

项目成果

Biodegradable xylitol-based elastomers: in vivo behavior and biocompatibility.

• DOI: 10.1002/jbm.a.32733
• 发表时间: 2010-10
• 期刊: JOURNAL OF BIOMEDICAL MATERIALS RESEARCH PART A
• 影响因子: 4.9
• 作者: Bruggeman, Joost P.;Bettinger, Christopher J.;Langer, Robert
• 通讯作者: Langer, Robert

Human embryonic stem cell-derived microvascular grafts for cardiac tissue preservation after myocardial infarction.

• DOI: 10.1016/j.biomaterials.2010.10.005
• 发表时间: 2011-03
• 期刊: Biomaterials
• 影响因子: 14
• 作者: Kraehenbuehl TP;Ferreira LS;Hayward AM;Nahrendorf M;van der Vlies AJ;Vasile E;Weissleder R;Langer R;Hubbell JA
• 通讯作者: Hubbell JA

Bioinspired materials for controlling stem cell fate.

• DOI: 10.1021/ar900226q
• 发表时间: 2010-03-16
• 期刊: ACCOUNTS OF CHEMICAL RESEARCH
• 影响因子: 18.3
• 作者: Fisher, Omar Z.;Khademhosseini, Ali;Langer, Robert;Peppas, Nicholas A.
• 通讯作者: Peppas, Nicholas A.

Cell-responsive hydrogel for encapsulation of vascular cells.

• DOI: 10.1016/j.biomaterials.2009.04.057
• 发表时间: 2009-09
• 期刊: BIOMATERIALS
• 影响因子: 14
• 作者: Kraehenbuehl, Thomas P.;Ferreira, Lino S.;Zammaretti, Prisca;Hubbell, Jeffrey A.;Langer, Robert
• 通讯作者: Langer, Robert

Biodegradable poly(polyol sebacate) polymers.

• DOI: 10.1016/j.biomaterials.2008.08.037
• 发表时间: 2008-12
• 期刊: BIOMATERIALS
• 影响因子: 14
• 作者: Bruggeman, Joost P.;de Bruin, Berend-Jan;Bettinger, Christopher J.;Langer, Robert
• 通讯作者: Langer, Robert