Completely biological tissue-engineered pulmonic valve grown in vitro from human

从人体体外培养的完全生物组织工程肺动脉瓣

• 批准号: 8083856
• 负责人: ROBERT T TRANQUILLO
• 金额: $ 56.87万
• 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/8083856
• 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; 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）：该研究计划的目标是将先前 NIH 资助所取得的进展转化为完全生物组织工程肺动脉瓣置换术，该置换术由成纤维细胞重塑的纤维蛋白在体外生长的组织制成。这将通过以下方式实现：（1）心脏瓣膜生物反应器设计和操作方面的进步，以加强根段和根-小叶附着线，以及（2）一种新的脱细胞和可选的再细胞化策略，使用间充质干细胞来消除植入后由于移植的成纤维细胞而发生的小叶收缩，这些成纤维细胞用于在体外生长组织瓣膜。这种组织工程心脏瓣膜（TEHV），包括脱细胞（依赖于宿主细胞侵袭）和再细胞化（植入前间充质干细胞），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 TEHV 随后能够改进以承受与主动脉瓣位置相关的力，那么成功最终将使美国每年约 10,000 名儿科患者受益，并最终使美国每年 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。 公共健康相关性：根据 AHA 的数据，仅在美国，每年就进行超过 95,000 例瓣膜置换手术。尽管机械和生物人工心脏瓣膜自 20 世纪 60 年代推出以来已经产生了巨大影响，但置换后 10 年死亡率仍为 30-55%。对于儿科患者来说，这种需求尤其巨大，因为这些瓣膜没有生长的能力。因此，人们对开发新一代组织工程心脏瓣膜产生了浓厚的兴趣，这项研究旨在设计和测试完全生物化的活瓣膜替代物。