PRIMATE MODEL EVALUATION OF A TISSUE ENGINEERED HEART VALVE

组织工程心脏瓣膜的灵长类动物模型评估

• 批准号: 8357672
• 负责人: Richard A Hopkins
• 金额: $ 0.1万
• 依托单位: TEXAS BIOMEDICAL RESEARCH INSTITUTE
• 依托单位国家: 美国
• 财政年份: 2011
• 资助国家: 美国
• 起止时间: 2011-05-01 至 2012-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8357672
• 关键词: Allografting; Biological; Biology; Cardiovascular system; Cells; Child; Chronic; Clinical; Complex; Engineering; Evaluation; Excision; Funding; Grant; Heart Valves; Human; Immune; Infant; Inflammatory; Lung; Mediating; Modeling; National Center for Research Resources; Papio; Patients; Performance; Primates; Principal Investigator; Process; Research; Research Infrastructure; Research Project Grants; Resources; Safety; Sheep; Source; Structural Protein; Testing; Therapeutic; Tissue Engineering; Translational Research; Transplantation; United States National Institutes of Health; Xenograft procedure; cost; design; immunogenic; in vivo; novel; preclinical safety; response; safety testing; scaffold; semilunar valve; tool; young adult

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. Primary support for the subproject and the subproject's principal investigator may have been provided by other sources, including other NIH sources. The Total Cost listed for the subproject likely represents the estimated amount of Center infrastructure utilized by the subproject, not direct funding provided by the NCRR grant to the subproject or subproject staff. This translational research project is prompted by the need to develop new evaluative tools to assess the preclinical safety of tissue engineered biological heart valves intended for use in infants, children and young adults. Chronic in vivo studies in sheep may not be sufficient to adequately evaluate primate-specific complex biology, immune and inflammatory-mediated responses that are critical factors expected to significantly impact the safety, performance and therapeutic durability of a tissue engineered biological heart valve for human clinical use. Such a tissue engineered cardiovascular construct, by definition, includes both cells (derived from the patient/recipient), and structural proteins (derived from the donor heart valve). The putative prototypical tissue engineered pulmonary valved conduit scaffold to be tested consists of either an allograft (homograft; ie, baboon species for orthotopic transplant) or a xenograft (human semilunar valve) scaffold. Both test valve types will have been engineered to effect removal of donor cells and reduce antigenicity (using our novel decellularization process). This design will test the safety of the acellular construct and the immunogenic and proinflammatory potential of allograft (papio) versus xenograft (human) structural proteins.

这个子项目是许多利用资源的研究子项目之一 由NIH/NCRR资助的中心拨款提供。子项目的主要支持 而子项目的主要调查员可能是由其他来源提供的， 包括其它NIH来源。 列出的子项目总成本可能 代表子项目使用的中心基础设施的估计数量， 而不是由NCRR赠款提供给子项目或子项目工作人员的直接资金。 该转化研究项目是由于需要开发新的评价工具来评估用于婴儿、儿童和年轻人的组织工程生物心脏瓣膜的临床前安全性。 绵羊的长期体内研究可能不足以充分评价灵长类动物特异性复杂生物学、免疫和炎症介导的反应，这些反应是预期会显著影响人类临床使用的组织工程生物心脏瓣膜的安全性、性能和治疗耐久性的关键因素。 根据定义，这种组织工程化心血管构建体包括细胞（来源于患者/受体）和结构蛋白（来源于供体心脏瓣膜）。 待测试的假定原型组织工程肺动脉瓣管道支架由同种异体移植物（同种移植物;即，用于原位移植的狒狒物种）或异种移植物（人半月瓣）支架组成。 两种试验瓣膜类型均经过工程设计，以实现供体细胞的去除并降低抗原性（使用我们的新型脱细胞工艺）。 该设计将测试无细胞构建体的安全性以及同种异体移植物（papio）与异种移植物（人）结构蛋白的免疫原性和促炎潜力。