Construction of a Portal Implantable Functional Tissue-Engineered Liver Using Perfusion-Decellularized Matrix and Hepatocytes in Rats
Construction of a Portal Implantable Functional Tissue-Engineered Liver Using Perfusion-Decellularized Matrix and Hepatocytes in Rats
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DOI：
10.3727/096368910x536572
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发表时间：
2011-01-01
影响因子：
3.3
通讯作者：
Bu, Hong
中科院分区：
文献类型：
--
作者：
Bao, Ji;Shi, Yujun;Bu, Hong
创新的基于细胞的疗法，包括肝细胞移植后的肝组织工程，被认为是肝移植或部分替代患者肝功能的理论替代方案。然而，肝组织工程的最新进展受到低初始肝细胞植入和体内血液供应不足的阻碍。我们开发了一个完整的3D支架的细胞外基质（ECM）来自脱细胞肝叶，与逐层（LbL）肝素沉积，以避免血栓形成，我们重新填充肝细胞，并成功植入作为组织工程肝脏（TEL）到门静脉系统。TEL提供了足够的体积，用于移植的细胞数量高达全肝当量的10%，并通过门静脉血液灌注。用TEL治疗延长的肝切除大鼠改善了肝功能并延长了生存期;平均寿命从16小时延长至72小时。术后72 h，TEL维持功能性和存活的肝细胞。总之，我们建议TEL作为全肝移植的最先进的替代品，并作为最终允许移植重建肝脏的技术的概念证明。
Innovative cell-based therapies, including hepatic tissue engineering following hepatocyte transplantation, are considered as theoretical alternatives to liver transplant or for partial replacement of liver function in patients. However, recent progress in hepatic tissue engineering has been hampered by low initial hepatocyte engraftment and insufficient blood supply in vivo. We developed an intact 3D scaffold of an extracellular matrix (ECM) derived from a decellularized liver lobe, with layer-by-layer (LbL) heparin deposition to avoid thrombosis, which we repopulated with hepatocytes and successfully implanted as a tissue-engineered liver (TEL) into the portal system. The TEL provided sufficient volume for transplantation of cell numbers representing up to 10% of whole-liver equivalents and was perfused by portal vein blood. Treatment of extended hepatectomized rats with a TEL improved liver function and prolonged survival; mean lifespan was extended from 16 to 72 h. At 72 h postoperation, the TEL sustained functional and viable hepatocytes. In conclusion, we propose the TEL as a state-of-the-art substitute for whole-liver transplantation and as a proof of concept for the technology that will eventually allow for the transplantation of a reconstituted liver.