Tissue-engineered pulmonic valve grown from human cells for pediatric patients

描述（由申请人提供）：本研究计划的目标是将先前NIH资助的进展转化为完全生物组织工程的肺瓣膜替代物，由成纤维细胞重塑的纤维蛋白体外培养的组织制成。这将通过(1)在心脏瓣膜生物反应器设计和操作方面的进步来实现，以加强根段和根-小叶的附着线；(2)利用间充质干细胞进行新的脱细胞和可选的再细胞化策略，以避免由于移植的成纤维细胞在植入后发生的小叶收缩，这些成纤维细胞用于体外培养组织瓣膜。这种组织工程心脏瓣膜（TEHV），包括脱细胞（依赖宿主细胞入侵）和再细胞（植入前的间充质干细胞），将在羔羊模型中进行验证，以证明工程瓣膜的生长能力和持续功能。如果该tev能够随后得到改善，以承受与主动脉瓣位置相关的力，那么成功将最终使美国每年大约10,000名儿科患者受益，最终使美国每年100,000名患者受益。与其他心血管组织工程应用相关的使能技术将作为这项研究的副产品产生。

DESCRIPTION (provided by applicant): The goal of this research plan is to translate the progress made with prior NIH funding into a completely biological tissue-engineered pulmonary valve replacement, made of tissue grown in vitro from fibroblast remodeled fibrin. This will be accomplished using (1) advances in heart valve bioreactor design and operation to strengthen the root segment and the root-leaflet attachment line, and (2) a new decellularization and optional recellularization strategy using mesenchymal stem cells to obviate the leaflet contraction that occurred post-implantation due to the transplanted fibroblasts, which are used to grow the tissue valve in vitro. This tissue-engineered heart valve (TEHV), both decellularized (relying on host cell invasion) and recellularized (with mesenchymal stem cells pre-implantation) will be validated in a lamb model to demonstrate growth capacity and sustained function of the engineered valve. Success will ultimately benefit approximately 10,000 pediatric patients in the U.S. annually and ultimately 100,000 patients in the U.S. annually if this TEHV can subsequently be improved to withstand forces associated with the aortic valve position. Enabling technologies relevant to other cardiovascular tissue engineering applications will be generated as a by-product of this research.