PRIMATE MODEL EVALUATION OF A TISSUE ENGINEERED HEART VALVE

这个子项目是许多研究子项目中的一个 由NIH/NCRR资助的中心赠款提供的资源。子项目和 研究者（PI）可能从另一个NIH来源获得了主要资金， 因此可在其他CRISP条目中表示。所列机构为 研究中心，而研究中心不一定是研究者所在的机构。 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。

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. 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.