In Vitro Expansion of Primary Human Hepatocytes with Efficient Liver Repopulation Capacity
In Vitro Expansion of Primary Human Hepatocytes with Efficient Liver Repopulation Capacity
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具有高效肝脏再生能力的原代人肝细胞的体外扩增
DOI：
10.1016/j.stem.2018.10.018
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发表时间：
2018-12-06
期刊：
影响因子：
23.9
通讯作者：
Hui, Lijian
中科院分区：
文献类型：
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作者：
Zhang, Kun;Zhang, Ludi;Hui, Lijian
人肝细胞移植(HHS)在治疗肝病方面具有巨大的潜力。然而，可移植的HHS的供应受到供体有限和体外扩增能力的严重限制。作为对慢性损伤的反应，一些HHS被重新编程为同时表达肝细胞和祖细胞标志的增殖细胞，这表明在体外扩增HHS的策略是可行的。在这里，我们报告了允许HHS扩大10,000倍的定义的中等条件。这些增殖的HHS是双表型的，部分保留了肝脏的特征，同时获得了祖细胞相关基因的表达。重要的是，这些细胞移植到受损的小鼠肝脏的水平与原始HHS相当，它们在体内移植或体外分化后会成熟。因此，本研究提供了一种能够大规模扩展可移植HHS的方案，该方案可以进一步开发用于模拟和治疗人类肝病。
Transplantation of human hepatocytes (HHs) holds significant potential for treating liver diseases. However, the supply of transplantable HHs is severely constrained by limited donor availability and compromised capacity for in vitro expansion. In response to chronic injury, some HHs are reprogrammed into proliferative cells that express both hepatocyte and progenitor markers, suggesting exploitable strategies for expanding HHs in vitro. Here, we report defined medium conditions that allow 10,000-fold expansion of HHs. These proliferating HHs are bi-phenotypic, partially retaining hepatic features while gaining expression of progenitor-associated genes. Importantly, these cells engraft into injured mouse liver at a level comparable to primary HHs, and they undergo maturation following transplantation in vivo or differentiation in vitro. Thus, this study provides a protocol that enables large-scale expansion of transplantable HHs, which could be further developed for modeling and treating human liver disease.