An Autologous, Culture-Free, Adipose Cell-Based Tissue Engineered Vascular Graft

一种自体、无培养、基于脂肪细胞的组织工程血管移植物

基本信息

批准号：
9015874
负责人：
David Alan Vorp
金额：
$ 19.18万
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：
2016
资助国家：
美国
起止时间：
2016-04-15 至 2018-03-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/9015874
关键词：
Acute Address Adipocytes Adipose tissue Animals Autologous Biological Bioreactors Blood Vessels Bypass Caliber Cardiovascular Diseases Cardiovascular system Cell Culture Techniques Cell Fraction Cells Clinic Clinical Collagen Culture Media Data Devices Elastin Endothelial Cells Evaluation Fatty acid glycerol esters Gold Harvest Homeostasis Hour Human Human Resources Implant In Vitro Lead Length Length of Stay Mechanics Mesenchymal Stem Cells Modeling Outcome Paired Comparison Patients Performance Pericytes Population Preparation Process Property Proteins Protocols documentation Rattus Risk Seeds Smooth Muscle Myocytes Source Stem cells Suction Lipectomy Technology Testing Time Tissue Engineering Tissues Translations Tubular formation Vacuum Vascular Graft Vascular Smooth Muscle Work base cell transformation cost design human subject implantation in vivo innovation new technology novel public health relevance research clinical testing scaffold scale up vascular tissue engineering

项目摘要

DESCRIPTION: Small-diameter tissue engineered vascular grafts (TEVGs) that incorporate autologous cells may provide an immuno-compatible treatment solution for patients with cardiovascular disease. We and others have shown that mesenchymal stem cells can promote remodeling of a biodegradable scaffold into native-like tissue that includes important vascular matrix proteins, such as collagen and elastin, and cells which contribute to vascular homeostasis, such as vascular smooth muscle cells and endothelial cells. Most recently, we have created TEVGs in this manner using adipose-derived mesenchymal stem cells from human donors. This application will address three critical barriers to translation of our current TEVG technology to the clinic. First, in our current TEVG paradigm, adipose-derived stem cells (AD-MSCs) are culture-expanded before seeding into biodegradable scaffolds. This presents a concern for the cells transforming or becoming contaminated, and also could represent significant costs with respect to personnel and materials. In addition, the presence of animal-sourced culture media supplements is a regulatory hurdle for any biological technology. Second, while the dynamic culture of a seeded graft for 48 hours - also part of our current TEVG protocol - is rapid compared to alternate approaches, it carries the same costs and risks as stated above for cell culture. Finally, our current TEVG has been optimized as an aortic interposition graft in the rat. Creating "human-sized" TEVG constructs for clinical translation wil require "scale-up" of at least one important process: seeding of cells into the scaffold. To address these concerns and advance our TEVG technology closer toward clinical feasibility, we propose the following three Specific Aims: 1) Evaluate the potential of using cells directly harvested from the stromal vascular fraction (SVF) immediately following liposuction (i.e., without time in culture) for fabricating our TEVG; 2) Eliminate the need for in-vitro bioreactor culture of our seeded construct to yield a TEVG that is safely and rapidly fabricated and ready to implant; and 3) Develop a new bulk-seeding device with the ability to deliver cells at high efficiency into "human-sized" scaffolds. Upon completion of this study, we expect to have developed an innovative "bedside" TEVG fabrication strategy using an alternative human adipose-derived cell source and a novel bulk-seeding device for long tubular scaffolds, and requiring no in vitro culture period. This will provide the basis of a new, innovative paradigm in vascular tissue engineering by eliminating significant regulatory barriers to clinical translation.

描述：包含自体细胞的小直径组织工程血管移植物（TEVG）可以为心血管疾病患者提供免疫相容的治疗解决方案，我们和其他人已经证明间充质干细胞可以促进可生物降解的支架重塑为类似天然的支架。包括重要的血管基质蛋白（例如胶原蛋白和弹性蛋白）以及有助于血管稳态的细胞（例如血管平滑肌细胞和内皮细胞）的组织。已经使用来自人类捐赠者的脂肪源间充质干细胞以这种方式创建了 TEVG，该应用将解决我们当前的 TEVG 技术转化为临床的三个关键障碍。 -MSC）在接种到可生物降解的支架之前进行培养扩增，这引起了细胞转化或被污染的担忧，并且还可能代表人员和材料方面的巨大成本。其次，虽然种子移植物的动态培养 48 小时（也是我们当前 TEVG 方案的一部分）与其他方法相比速度更快，但它具有相同的成本和成本。最后，我们目前的 TEVG 已被优化为大鼠的主动脉介入移植物，创建用于临床转化的“人体大小”TEVG 结构将需要“放大”至少一个重要过程：播种为了解决这些问题并使我们的 TEVG 技术更接近临床可行性，我们提出以下三个具体目标：1) 评估在吸脂后立即使用从基质血管部分 (SVF) 直接收获的细胞的潜力 (即无需培养时间）来制造我们的 TEVG；2）无需对我们的种子结构进行体外生物反应器培养，即可安全、快速地制造 TEVG并准备植入；3) 开发一种新的批量接种装置，能够高效地将细胞输送到“人体大小”的支架中。完成这项研究后，我们预计将开发出一种创新的“床边”TEVG 制造方法。该策略使用替代的人类脂肪来源的细胞来源和用于长管状支架的新型批量接种装置，并且不需要体外培养期，这将为血管组织工程中的新的、创新的范例消除显着的监管障碍奠定基础。到临床转化。