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

心血管组织工程（CVTE）是一个新兴的领域，其目标是基于工程和生物科学的原理，创造血管组织来恢复、维持或改善功能。该项目的主要目标是开发一种组织工程血管移植物。基于CVTE领域的知识现状，在理想的组织工程血管移植物的发展中可以概述几个目标。移植物应具有足够的强度，易于缝合，并能承受动脉压力。用于开发组织工程构建的细胞，特别是内皮细胞，应该是自体的，应该来自于供体部位发病率最低的成人。PI计划利用技术驱动多能细胞向平滑肌细胞和内皮细胞谱系发展。一旦这些细胞在各种可溶性化学因子的作用下分化，它们将被依次播种到多孔胶原泡沫上，并在脉动和剪切应力下培养。细胞/胶原结构将相对于静态对照进行评估，假设包含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。冠状动脉疾病可以通过各种介入手术治疗；然而，由于再狭窄，这些手术失败率很高，通常必须进行手术重建。导管通常从同一个人身上取出，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理想，目前没有可用的移植物来替代直径较小（4mm）的冠状动脉。开发一种由骨髓细胞改造而成的自体导管将挽救那些别无选择的病人的生命。

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.