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

由人体细胞培育而成的组织工程肺动脉瓣，供儿科患者使用

• 批准号: 8242099
• 负责人: ROBERT T TRANQUILLO
• 金额: $ 65.67万
• 依托单位: UNIVERSITY OF MINNESOTA
• 依托单位国家: 美国
• 财政年份: 2011
• 资助国家: 美国
• 起止时间: 2011-04-01 至 2016-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8242099
• 关键词: Adolescent; Adult; Animal Model; Benchmarking; Biological; Bioprosthesis device; Bioreactors; Caliber; Cardiovascular system; Cells; Childhood; Clinical Trials; Culture Media; Data; Deposition; Dermal; Development; Diffusion; Engineering; Exhibits; Failure; Feedback; Fibrin; Fibroblasts; Funding; Gel; Generations; Goals; Growth; Heart Valves; Hematopoietic; Human; Implant; In Vitro; Infiltration; Life; Mechanics; Mesenchymal Stem Cells; Modeling; Monitor; Nutrient; Operative Surgical Procedures; Patients; Performance; Phenotype; Physiologic pulse; Plant Roots; Polymers; Positioning Attribute; Property; Pulmonary artery structure; Pulmonary valve structure; Pump; Radial; Research; Seeds; Sheep; Silicones; Smooth Muscle Actin Staining Method; Stretching; Stroke Volume; Surface; Technology; Tensile Strength; Testing; Thinness; Tissue Engineering; Tissues; Translating; Transplantation; Tube; United States; United States National Institutes of Health; Validation; Variant; aortic valve; aortic valve replacement; design; human tissue; implantation; improved; interest; mortality; operation; pre-clinical; preimplantation; pressure; public health relevance; pulmonary valve replacement; success; valve replacement

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. PUBLIC HEALTH RELEVANCE: In the United States alone, over 95,000 valve replacement surgeries are now performed annually according to the AHA. While mechanical and bioprosthetic heart valves have made a dramatic impact since their introduction in the 1960's, the 10-year mortality after replacement is still 30-55%. The need is particularly great for pediatric patients, since these valves do not have the capacity to grow. Thus, there is great interest in developing a new generation of tissue-engineered heart valves and this research is aimed at the design and testing of a completely biological living valve replacement.

描述（由申请人提供）：本研究计划的目的是将先前的NIH资金进行的进度转化为完全生物组织工程的肺动脉瓣，由成纤维细胞重塑的纤维蛋白在体外生长的组织制成。这将使用（1）心脏瓣膜生物反应器设计和操作的进步来增强根部段和根叶的附着线，以及（2）使用间质干细胞的新脱细胞和可选的卷积策略来避免传单后植入后植入后因纤维纤维而生长的植入术后的植入后，该策略与组织相结合，以生长，从而成长，以生长，以至于散发出来，从而在组织中成长，以使其成长。该组织工程的心脏瓣膜（TEHV），脱细胞（依赖于宿主细胞的侵袭）和较细胞化的（带有间充质干细胞）将在羊羔模型中验证，以证明生长能力和工程瓣膜的持续功能。如果随后可以改善该TEHV，则最终将每年在美国和美国最终100,000名患者中，成功最终将使美国的儿科患者受益，并最终受益于美国的100,000名患者。与其他心血管组织工程应用相关的促成技术将作为本研究的副产品生成。 公共卫生相关性：仅在美国，根据AHA，现在每年进行超过95,000个阀门置换手术。自从1960年代引入以来，机械和生物假发心脏瓣膜产生了巨大的影响，但替换后的10年死亡率仍为30-55％。对于儿科患者而言，需求特别伟大，因为这些瓣膜没有生长能力。因此，人们对开发新一代组织工程心脏瓣膜有很大的兴趣，这项研究旨在设计和测试完全生物生物的替代品。