Expansion of human primary hepatocytes in vitro through their amplification as liver progenitors in a 3D organoid system.
Expansion of human primary hepatocytes in vitro through their amplification as liver progenitors in a 3D organoid system.
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DOI：
10.1038/s41598-018-26584-1
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发表时间：
2018-05-29
影响因子：
4.6
通讯作者：
Nguyen TH
中科院分区：
文献类型：
--
作者：
Garnier D;Li R;Delbos F;Fourrier A;Collet C;Guguen-Guillouzo C;Chesné C;Nguyen TH
尽管对成人原代肝细胞的增殖进行了数十年的研究，但它们的体外扩增仍然具有挑战性。为了以后能够考虑将肝细胞作为细胞疗法的替代方案或肝移植的桥梁，由于肝脏供体的短缺而受到极大阻碍，第一步是拥有几乎无限的这些细胞来源。可移植肝细胞的储存还意味着其扩增方案可以与大规模生产兼容。我们证明，在 3D 类器官中生长的成人原代肝细胞很容易扩增，为移植提供了充足的功能性肝细胞来源。铺板后，分化的人肝细胞在短暂且可逆的步骤中作为肝祖细胞被扩增，并且随后可以转化回成熟的分化肝细胞。由于悬浮中肝细胞的扩增，我们提出的方案不仅与自动化和高通量细胞培养系统兼容，而且还保证从同一患者样本中产生大量功能细胞，且设置相对简单。
Despite decades of investigation on the proliferation of adult human primary hepatocytes, their expansion in vitro still remains challenging. To later be able to consider hepatocytes as a cell therapy alternative or bridge to liver transplantation, dramatically impeded by a shortage in liver donors, the first step is having an almost unlimited source of these cells. The banking of transplantable hepatocytes also implies a protocol for their expansion that can be compatible with large-scale production. We show that adult human primary hepatocytes when grown in 3D organoids are easily amplified, providing a substantial source of functional hepatocytes ready for transplantation. Following their plating, differentiated human hepatocytes are amplified during a transient and reversible step as liver progenitors, and can subsequently be converted back to mature differentiated hepatocytes. The protocol we propose is not only compatible with automated and high-throughput cell culture systems, thanks to the expansion of hepatocytes in suspension, but also guarantees the generation of a high number of functional cells from the same patient sample, with a relatively easy set up.
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