Transplantation of bioengineered liver capable of extended function in a preclinical liver failure model.

Transplantation of bioengineered liver capable of extended function in a preclinical liver failure model.
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DOI:
10.1111/ajt.16928
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发表时间:
2022-03
期刊:
American journal of transplantation : official journal of the American Society of Transplantation and the American Society of Transplant Surgeons
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其他
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无限的器官供应将代表移植的范式转变。长期在体内植入和功能的放大生物工程肝移植以前没有报道。在这项研究中,我们描述了一个人类规模的可移植肝脏移植物上的猪肝衍生支架工程。我们用原代肝细胞重新填充支架实质,用内皮细胞重新填充血管系统。对于体内功能测试,我们在诱导肝衰竭的猪中进行了再填充支架的辅助移植。据观察,辅助生物工程肝移植物改善肝功能28天,并表现出肝脏特异性基因的上调。这项研究是第一个使用临床前大型动物模型对生物工程肝移植物进行移植后28天评估的研究。此外,它提供了明确的证据,工程人类规模的可移植肝移植的临床应用的可行性。
Unlimited organ availability would represent a paradigm shift in transplantation. Long-term in vivo engraftment and function of scaled-up bioengineered liver grafts have not been previously reported. In this study, we describe a human-scale transplantable liver graft engineered on a porcine liver-derived scaffold. We repopulated the scaffold parenchyma with primary hepatocytes and the vascular system with endothelial cells. For in vivo functional testing, we performed auxiliary transplantation of the repopulated scaffold in pigs with induced liver failure. It was observed that the auxiliary bioengineered liver graft improved liver function for 28 days and exhibited upregulation of liver-specific genes. This study is the first of its kind to present 28 days of posttransplant evaluation of a bioengineered liver graft using a preclinical large animal model. Furthermore, it provides definitive evidence for the feasibility of engineering human-scale transplantable liver grafts for clinical applications.
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