ADVANCE Fellows Award: The Development of a Tissue-Engineered Vascular Graft from Multipotent Adult Progenitor Cells

0137590建议心血管组织工程（CVTE）是一个新兴的领域，其目标是根据工程学和生物科学的原理创造恢复、维持或改善功能的血管组织。 本研究的主要目的是开发一种组织工程化的血管移植物。 基于CVTE领域的当前知识状态，在理想的组织工程化血管移植物的开发中可以概述几个目标。 移植物应具有足够的强度，易于缝合并承受动脉压。用于开发组织工程构建体的细胞，特别是内皮细胞，应该是自体的，并且应该来自供体部位发病率最低的成年个体。PI计划利用技术将多能细胞驱动到平滑肌细胞和内皮细胞谱系。 一旦这些细胞已经使用各种可溶性化学因子分化，它们将依次接种到多孔胶原泡沫上，并在脉动和剪切应力下培养。 将相对于静态对照来评价细胞/胶原构建物，假设构成移植物的细胞的分化表型和移植物本身的强度可以通过化学和机械刺激的组合来控制和维持。然而，由于再狭窄，这些手术具有很高的失败率，并且通常必须进行外科重建。 导管通常从同一个人身上取出，并用作受影响动脉周围的旁路。 有些人有不合适的动脉或静脉，因为静脉曲张，分支，或管腔大小不足。 如果这些自体导管不可用或状况不令人满意，则目前没有可用的移植物来替代小直径（4 mm）冠状动脉。 开发一种由骨髓细胞改造的自体管道将挽救那些没有其他选择的患者的生命。

0137590 Suggs Cardiovascular tissue engineering (CVTE) is an emerging field with the goal of creating vascular tissues that restore, maintain, or improve function based on the principles of engineering and the biologic sciences. The primary goal of this project is to develop a tissue-engineered vascular graft. Based on the current state of knowledge in the field of CVTE, several objectives can be outlined in the development of an ideal tissue-engineered vascular graft. The graft should have sufficient strength to be easily sutured and withstand arterial pressures. The cells used in developing the tissue-engineered construct, particularly endothelial cells, should be autologous and should be derived from adult individuals with minimal donor site morbidity.The PI plans to utilize techniques to drive multipotent cells towards smooth muscle cell and endothelial cell lineages. Once these cells have been differentiated using various soluble chemical factors, they will be seeded sequentially onto porous collagen foams and cultured under both pulsatile and shear stresses. The cell/collagen constructs will be evaluated relative to static controls with the hypothesis that the differentiated phenotype of the cells comprising the graft and the strength of the graft itself can be controlled and maintained by a combination of both chemical and mechanical stimulation.Coronary artery disease can be treated with various interventional procedures; however, these procedures have a high failure rate due to restenosis and often must be followed by surgical reconstruction. Conduits are typically removed from the same individual and used as a bypass around the affected artery. Some individuals have unsuitable arteries or veins because of varicosities, branching, or inadequate lumen size. If these autologous conduits are not available or not in satisfactory condition, there are no currently available grafts to replace the small diameter (4mm) coronary arteries. The development of an autologous conduit engineered from bone marrow cells would save the lives of patients who have no other options.