Vascularized organoid engineered by modular assembly enables blood perfusion
Vascularized organoid engineered by modular assembly enables blood perfusion
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DOI：
10.1073/pnas.0602740103
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发表时间：
2006-08-01
影响因子：
11.1
通讯作者：
Sefton, Michael V.
中科院分区：
文献类型：
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作者：
McGuigan, Alison P.;Sefton, Michael V.
组织工程是解决供体器官短缺问题的一种方法，但为了在厚组织中获得临床上显着的活细胞密度，实验室构建的组织必须具有内部血管供应。我们采用仿生方法并组装了微型模块化组件，其中包括亚毫米大小的胶原凝胶棒，其中将内皮细胞（EC）植入（微）血管化组织中；在一些原型中，凝胶含有 HepG2 细胞以说明这种可能性。然后将 EC 覆盖的模块组装到更大的管中并用培养基或全血灌注。模块之间的间隙空间形成了互连的通道，从而实现了这种灌注。活细胞密度很高，在组织内细胞密度的一个数量级内，并且在微计算机断层扫描和多普勒超声测量中，流经构建体的渗透性质很明显。最重要的是，ECS 保留了其非血栓形成表型，延迟了凝血时间，并抑制了与通过该结构灌注全血相关的血小板损失。与其他组织工程方法的传统支架和细胞接种范例不同，这种模块化构造具有可扩展、均匀且可用全血灌注的潜力，从而规避了其他方法的局限性。
Tissue engineering is one approach to address the donor-organ shortage, but to attain clinically significant viable cell densities in thick tissues, laboratory-constructed tissues must have an internal vascular supply. We have adopted a biomimetic approach and assembled microscale modular components, consisting of submillimeter-sized collagen gel rods seeded with endothelial cells (ECs) into a (micro)vascularized tissue; in some prototypes the gel contained HepG2 cells to illustrate the possibilities. The EC-covered modules then were assembled into a larger tube and perfused with medium or whole blood. The interstitial spaces among the modules formed interconnected channels that enabled this perfusion. Viable cell densities were high, within an order of magnitude of cell densities within tissues, and the percolating nature of the flow through the construct was evident in microcomputed tomography and Doppler ultrasound measurements. Most importantly, the ECS retained their nonthrombogenic phenotype and delayed clotting times and inhibited the loss of platelets associated with perfusion of whole blood through the construct. Unlike the conventional scaffold and cell-seeding paradigm of other tissue-engineering approaches, this modular construct has the potential to be scalable, uniform, and perfusable with whole blood, circumventing the limitations of other approaches.