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

基本信息

批准号：
8649073
负责人：
ROBERT T TRANQUILLO
金额：
$ 69.42万
依托单位：
UNIVERSITY OF MINNESOTA
依托单位国家：
美国
项目类别：
财政年份：
2011
资助国家：
美国
起止时间：
2011-04-01 至 2016-08-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/8649073
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

项目摘要

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.

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小叶收缩，由于移植的成纤维细胞用于在体外生长组织瓣膜，因此发生在植入后。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。