Inflammatory Cytokine TNFα Promotes the Long-Term Expansion of Primary Hepatocytes in 3D Culture.
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Title | Inflammatory Cytokine TNFα Promotes the Long-Term Expansion of Primary Hepatocytes in 3D Culture. |
Publication Type | Journal Article |
Year of Publication | 2018 |
Authors | Peng WC, Logan CY, Fish M, Anbarchian T, Aguisanda F, Álvarez-Varela A, Wu P, Jin Y, Zhu J, Li B, Grompe M, Wang B, Nusse R |
Journal | Cell |
Volume | 175 |
Issue | 6 |
Pagination | 1607-1619.e15 |
Date Published | 2018 Nov 29 |
ISSN | 0092-8674 |
Abstract | In the healthy adult liver, most hepatocytes proliferate minimally. However, upon physical or chemical injury to the liver, hepatocytes proliferate extensively in vivo under the direction of multiple extracellular cues, including Wnt and pro-inflammatory signals. Currently, liver organoids can be generated readily in vitro from bile-duct epithelial cells, but not hepatocytes. Here, we show that TNFα, an injury-induced inflammatory cytokine, promotes the expansion of hepatocytes in 3D culture and enables serial passaging and long-term culture for more than 6 months. Single-cell RNA sequencing reveals broad expression of hepatocyte markers. Strikingly, in vitro-expanded hepatocytes engrafted, and significantly repopulated, the injured livers of Fah mice. We anticipate that tissue repair signals can be harnessed to promote the expansion of otherwise hard-to-culture cell-types, with broad implications. |
URL | https://linkinghub.elsevier.com/retrieve/pii/S0092-8674(18)31504-6 |
DOI | 10.1016/j.cell.2018.11.012 |
Short Title | Cell |