Generating Vascular Graft Luminal and Medial Layers Based on Multipotent Stem Cel

基于多能干细胞生成血管移植管腔和内侧层

基本信息

批准号：
8692757
负责人：
Mariah S Hahn
金额：
$ 7.77万
依托单位：
RENSSELAER POLYTECHNIC INSTITUTE
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：
2013-07-01 至 2015-06-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/8692757
关键词：
Address Adhesions Adipose tissue Adult Affect American Arteries Autologous Blood Vessels Caliber Cardiovascular Diseases Cell Culture Techniques Cell Differentiation process Cell Line Cells Clinical Coronary Arteriosclerosis Coronary artery Data Deposition Development Drug Formulations Emergency Situation Endothelial Cells Ethylene Glycols Extracellular Matrix Failure Future Gel Growth Factor Health Human Hydrogels Insulin-Like Growth Factor I Integrins Mechanics Medial Mesenchymal Stem Cells Operative Surgical Procedures Patients Peptides Pericytes Peripheral Peripheral arterial disease Phenotype Platelet Activation Platelet aggregation Polytetrafluoroethylene Procedures Process Production Property Prosthesis Relative (related person)Signal Transduction Smooth Muscle Myocytes Stem cells Structure Tissue Engineering Tissues United States Vascular Endothelial Cell Vascular Endothelial Growth Factors Vascular Graft base cell behavior design ethylene glycol implantation innovation mortality multipotent cell novel strategies preimplantation public health relevance response stem stem cell differentiation success

项目摘要

DESCRIPTION (provided by applicant): In the US alone, approximately 1.4 million patients require small-caliber (< 6 mm ID) coronary artery or peripheral vessel grafts each year. Over 10% of these patients have no suitable autologous vessels for grafting. However, current synthetic prostheses, such as expanded polytetrafluoroethylene (ePTFE) grafts, display high failure rates in small-diameter applications. Tissue engineered vascular grafts (TEVGs) are therefore being actively developed for small-caliber applications. Although significant progress has been made, TEVG clinical viability has been hampered by: 1) thrombogenicity resulting from inadequate endothelialization, 2) the frequent need for pre-implantation cell and/or construct culture, 3) short- and long-term compliance mismatch between graft and host tissue, and 4) inadequate long-term mechanical strength resulting from insufficient neomatrix deposition by associated cells. We propose to address these limitations by developing a multilayered vascular graft (MLVG) which: 1) allows immediate formation of a stable, luminal cell lining for short- and long-term thromboresistance, 2) incorporates medial and luminal hydrogel layers specifically designed to direct human adipose-derived mesenchymal stem cells (ASCs) toward vascular smooth muscle cell (VSMC) or endothelial cell (EC) fates, respectively, 3) combines these hydrogels with a central electrospun mesh designed for short-term compliance-matching, and 4) includes an electrospun sleeve providing for burst strength, adventitial cell recruitment, and vaso vasorum ingrowth. The proposed studies will focus on developing the proposed medial and luminal hydrogel layers. Towards this end, we will execute the following Specific Aims: AIM 1: Identify growth-factor laden, PEG hydrogel formulations inductive of ASC differentiation into VSMC-like phenotypes and medial layer-appropriate extracellular matrix synthesis. AIM 2: Identify growth factor-laden, PEG "cement" formulations that promote ASC differentiation into EC-like phenotypes.

描述（由申请人提供）：仅在美国，大约有140万患者需要每年小疗效（<6 mm ID）冠状动脉或外围血管移植物。超过10％的患者没有合适的自体血管进行嫁接。然而，当前的合成假体，例如扩展的聚氟乙烯（EPTFE）移植物，在小直径应用中显示出较高的失败率。因此，组织工程的血管移植物（TEVG）是针对小疗程的应用而积极开发的。尽管已经取得了重大进展，但TEVG临床生存能力受到以下方面的阻碍：1）由内皮化不足导致的血栓形成性，2）经常需要对植入前细胞和/或构建培养的需求，3）长期和宿主组织之间的短期和长期不匹配，以及4）长期的机械强度不足。 We propose to address these limitations by developing a multilayered vascular graft (MLVG) which: 1) allows immediate formation of a stable, luminal cell lining for short- and long-term thromboresistance, 2) incorporates medial and luminal hydrogel layers specifically designed to direct human adipose-derived mesenchymal stem cells (ASCs) toward vascular smooth muscle cell (VSMC) or endothelial cell (EC)命运分别为3）将这些水凝胶与专为短期合规性匹配设计的中央电气传播网格结合在一起，4）包括一个电纺套筒，可提供爆发强度，外胞体细胞募集和Vaso vasorum vasorum infrowth。拟议的研究将着重于开发提出的内侧水凝胶层。为此，我们将执行以下特定目的：目标1：确定载体，PEG水凝胶配方的ASC分化为VSMC样表型和内侧层 - 适合细胞外基质合成。 AIM 2：确定富含生长因子的钉子“水泥”制剂，可促进ASC分化为EC样表型。