Autologous Stem Cell-Based Tissue Engineered Vascular Grafts

基于自体干细胞的组织工程血管移植物

基本信息

批准号：
8426531
负责人：
David Alan Vorp
金额：
$ 19.06万
依托单位：
UNIVERSITY OF PITTSBURGH AT PITTSBURGH
依托单位国家：
美国
项目类别：
财政年份：
2013
资助国家：
美国
起止时间：
2013-01-15 至 2014-12-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/8426531
关键词：
Address Adipose tissue Adult Affect Age Area Arteries Autologous Binding Biocompatible Biocompatible Materials Biomechanics Biomimetics Blood Vessels Bone Marrow Bypass Cardiovascular Diseases Cells Clinical Coronary Artery Bypass Development Effectiveness Elderly Exhibits Fatty acid glycerol esters Female Goals Harvest Human Immune Institutes Laboratories Medicine Mesenchymal Stem Cells Methodology Methods Modeling Muscle Natural regeneration Organ Transplantation Outcome Patients Performance Peripheral Process Rattus Regenerative Medicine Relative (related person)Research Personnel Resources Scientific Societies Secure Shapes Solutions Source Stem cells Technology Testing Tissue Engineering Tissues Translations Treatment Efficacy United States National Institutes of Health Ursidae Family Vascular Graft Vascular remodeling Veins Venous Work base cost effective density elastomeric human adult stem cell human stem cells immunosuppressed in vivo in vivo Model innovation male novel patient population prevent public health relevance regenerative response scaffold sex stem cell biology success therapy development

项目摘要

DESCRIPTION (provided by applicant): There is a significant need for a successful vascular graft for the nearly one million aortocoronary bypass, peripheral arterial bypass, and arterio-venous access graft procedures performed each year in the US, as current clinical options are unreliable. The overall goal of this R21 proposal is to begin the process of clinical translation o our novel, autologous, stem cell-based tissue engineered vascular graft (TEVG) by addressing critical issues of practical implementation and rate-limiting barriers that have prevented current paradigms from being successful. This proposal will focus on use of adipose-derived stem cells (ADSCs), given the relative ease of isolation and availability of fat in the patient population in need. The following important issues/questions will be addressed in this proposal: A) Autologous adult ADSCs isolated in a typical single harvest from a patient are limited in number. What is the lower bound of ADSC seeding density necessary to yield a successful TEVG? B) Age and sex have both been shown to influence cardiovascular disease development and treatment efficacy. Will a stem cell-based TEVG using ADSCs from all patients be feasible, or will certain factors (e.g., male or female sex, patients beyond a certain age) preclude this therapy? Accordingly, the two specific aims of this 2-year proposal are: 1) Assess the effect of ADSC seeding density on the performance of TEVG constructs tested in a rat model; and 2) Assess the effect of donor age and sex in a rat model of the same sex on in-vivo performance of human cell-based TEVG constructs. The expected outcome of this work is an important step toward the successful development of a human stem cell-based TEVG, moving it significantly closer to clinical translation. No other study, to our knowledge, has addressed critical issues of clinical practicality, such as those to be addressed here, for the development of a human, stem cell-based TEVG.

描述（由申请人提供）：美国每年进行近百万例主动脉冠状动脉搭桥手术、外周动脉搭桥手术和动静脉通路移植手术，迫切需要成功的血管移植手术，因为目前的临床选择并不可靠。该 R21 提案的总体目标是通过解决实际实施的关键问题和阻碍当前范式的速率限制障碍，开始我们新型自体干细胞组织工程血管移植物 (TEVG) 的临床转化过程。正在成功。鉴于脂肪在有需要的患者群体中相对容易分离和可用性，该提案将重点关注脂肪干细胞（ADSC）的使用。本提案将解决以下重要问题：A) 在典型的单次收获中从患者身上分离出的自体成人 ADSC 数量有限。产生成功的 TEVG 所需的 ADSC 接种密度下限是多少？ B) 年龄和性别均已被证明会影响心血管疾病的发展和治疗效果。使用所有患者的 ADSC 进行基于干细胞的 TEVG 是否可行，或者某些因素（例如男性或女性、超过一定年龄的患者）会妨碍这种治疗吗？因此，这个为期 2 年的提案的两个具体目标是： 1) 评估 ADSC 接种密度对大鼠模型中测试的 TEVG 结构性能的影响； 2) 评估同性大鼠模型中供体年龄和性别对基于人类细胞的 TEVG 构建体体内性能的影响。这项工作的预期结果是成功开发基于人类干细胞的 TEVG 的重要一步，使其更接近临床转化。据我们所知，没有其他研究能够解决临床实用性的关键问题，例如本文要解决的用于开发人类干细胞 TEVG 的问题。