Scaffold-free, Human Mesenchymal Stem Cell-Based Tissue Engineered Blood Vessels.
Scaffold-free, Human Mesenchymal Stem Cell-Based Tissue Engineered Blood Vessels.
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DOI：
10.1038/srep15116
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发表时间：
2015-10-12
影响因子：
4.6
通讯作者：
Leong KW
中科院分区：
文献类型：
--
作者：
Jung Y;Ji H;Chen Z;Fai Chan H;Atchison L;Klitzman B;Truskey G;Leong KW
组织工程血管（TEBV）可以作为血管移植物，也可能在器官芯片的发展中发挥重要作用。大多数TEBV构建涉及用生物材料如胶原凝胶或电纺纤维网构建支架。假设无支架的TEBV可能是有利的，我们构建了管状结构（Imm i. d.）由排列的人间充质细胞片（hMSC）作为壁和人内皮祖细胞（hEPC）涂层作为内腔。在旋转壁生物反应器中连续培养三周并以6.8达因/cm 2灌注后，无支架TEBV的爆破压力高于200 mmHg。基于hMSC的TEBV的细胞层的交织组织和广泛的细胞外基质（ECM）形成类似于天然血管。TEBV在1 μM苯肾上腺素作用下表现出与猪股静脉相似的血流介导的血管舒张、收缩和一氧化氮释放。HL-60细胞在TNF-α活化后附着于TEBV管腔，表明内皮功能正常。该研究证明了hEPC内皮化的基于hMSC的TEBV用于药物筛选的潜力。
Tissue-engineered blood vessels (TEBV) can serve as vascular grafts and may also play an important role in the development of organs-on-a-chip. Most TEBV construction involves scaffolding with biomaterials such as collagen gel or electrospun fibrous mesh. Hypothesizing that a scaffold-free TEBV may be advantageous, we constructed a tubular structure (1 mm i.d.) from aligned human mesenchymal cell sheets (hMSC) as the wall and human endothelial progenitor cell (hEPC) coating as the lumen. The burst pressure of the scaffold-free TEBV was above 200 mmHg after three weeks of sequential culture in a rotating wall bioreactor and perfusion at 6.8 dynes/cm2. The interwoven organization of the cell layers and extensive extracellular matrix (ECM) formation of the hMSC-based TEBV resembled that of native blood vessels. The TEBV exhibited flow-mediated vasodilation, vasoconstriction after exposure to 1 μM phenylephrine and released nitric oxide in a manner similar to that of porcine femoral vein. HL-60 cells attached to the TEBV lumen after TNF-α activation to suggest a functional endothelium. This study demonstrates the potential of a hEPC endothelialized hMSC-based TEBV for drug screening.