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首页> 外文期刊>Artificial Organs >Discarded Livers Find a New Life: Engineered Liver Grafts Using Hepatocytes Recovered From Marginal Livers
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Discarded Livers Find a New Life: Engineered Liver Grafts Using Hepatocytes Recovered From Marginal Livers

机译：被丢弃的肝脏发现新的生活：使用从边缘肝脏恢复的肝细胞的工程肝移植物

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摘要

Treatment for end-stage liver failure is restricted by the critical shortage of donor organs; about 4000 people die in the USA while waiting for a transplantable organ. This situation has been a major driving force behind the rise of tissue engineering to build artificial tissues/organs. Recent advancements in creating transplantable liver grafts using decellularized liver scaffolds bring the field closer to clinical translation. However, a source of readily available and highly functional adult hepatocytes in adequate numbers for regenerative liver therapies still remains unclear. Here, we describe a new method to utilize discarded livers to make transplantable new liver grafts. We show that marginal donor livers damaged due to warm ischemia could be treated with machine perfusion to yield 39 million viable hepatocytes per gram of liver, similar to fresh livers, and these cells could be used to repopulate decellularized liver matrix (DLM) scaffolds to make transplantable liver grafts. The hepatocytes from recovered livers sustained their characteristic epithelial morphology while they exhibited slightly lower protein synthesis functions both in plate cultures and in recellularized liver grafts. The dampened protein synthesis was attributed to residual endoplasmic reticulum stress found in recovered cells. The results here represent a unique approach to reengineer transplantable liver grafts solely from discarded organs.
机译：终级肝衰竭的治疗受供体器官的关键短缺限制;在等待移植器官时，大约4000人死亡。这种情况一直是组织工程崛起的主要动力，以建立人工组织/器官。使用脱细胞肝脏脚手架产生可移植肝移植物的最新进展使该领域更接近临床翻译。然而，用于再生肝脏疗法的足够数量的容易可获得和高官能的成人肝细胞的来源仍然尚不清楚。在这里，我们描述了一种利用丢弃的肝脏来使可移植的新肝移植物的新方法。我们表明，由于温暖的缺血因机器灌注而损坏的边缘供体肝脏可以治疗每克肝脏，类似于新鲜肝脏的3900万可行的肝细胞，这些细胞可用于汇集脱叶肝脏基质（DLM）支架以制造可移植的肝移植物。来自回收的肝脏的肝细胞持续其特征上皮形态，同时它们在板培养物和翻透话的肝移植物中表现出稍微低下的蛋白质合成函数。抑制蛋白质合成归因于回收细胞中发现的残留内质网胁迫。这里的结果代表了单独从废弃的器官中再生可移植的肝移植物的独特方法。

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