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利用整个器官脱细胞技术生成血管化的肝类器官。

The use of whole organ decellularization for the generation of a vascularized liver organoid.

机构信息

Wake Forest Institute for Regenerative Medicine, Wake Forest University School of Medicine, Winston-Salem, NC 27157, USA.

出版信息

Hepatology. 2011 Feb;53(2):604-17. doi: 10.1002/hep.24067. Epub 2011 Jan 10.

Abstract

UNLABELLED

A major roadblock to successful organ bioengineering is the need for a functional vascular network within the engineered tissue. Here, we describe the fabrication of three-dimensional, naturally derived scaffolds with an intact vascular tree. Livers from different species were perfused with detergent to selectively remove the cellular components of the tissue while preserving the extracellular matrix components and the intact vascular network. The decellularized vascular network was able to withstand fluid flow that entered through a central inlet vessel, branched into an extensive capillary bed, and coalesced into a single outlet vessel. The vascular network was used to reseed the scaffolds with human fetal liver and endothelial cells. These cells engrafted in their putative native locations within the decellularized organ and displayed typical endothelial, hepatic, and biliary epithelial markers, thus creating a liver-like tissue in vitro.

CONCLUSION

These results represent a significant advancement in the bioengineering of whole organs. This technology may provide the necessary tools to produce the first fully functional bioengineered livers for organ transplantation and drug discovery.

摘要

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成功进行器官生物工程的主要障碍是需要在工程组织内建立功能性血管网络。在这里,我们描述了具有完整血管树的三维天然衍生支架的制造。来自不同物种的肝脏用去污剂灌注,以选择性地去除组织的细胞成分,同时保留细胞外基质成分和完整的血管网络。脱细胞血管网络能够承受通过中央入口进入的流体流动,分支成广泛的毛细血管床,并合并成单个出口血管。血管网络用于将人胎肝和内皮细胞重新播种到支架中。这些细胞在脱细胞器官的固有位置植入,并显示出典型的内皮、肝脏和胆管上皮标记物,从而在体外产生类似肝脏的组织。

结论

这些结果代表了整个器官生物工程的重大进展。这项技术可能为生产第一个完全功能性的生物工程肝脏用于器官移植和药物发现提供必要的工具。

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