Inflammatory Cytokine TNFα Promotes the Long-Term Expansion of Primary Hepatocytes in 3D Culture
| Autor: | Catriona Y. Logan, Adrián Álvarez-Varela, Francis Aguisanda, Bruce Wang, Bin Li, Markus Grompe, Teni Anbarchian, Roel Nusse, Yinhua Jin, Matt Fish, Junjie Zhu, Weng Chuan Peng, Peng Wu |
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| Rok vydání: | 2018 |
| Předmět: |
0301 basic medicine
Time Factors medicine.medical_treatment Cell Culture Techniques Medical and Health Sciences Oral and gastrointestinal Mice TNFα Cell Line Transformed Mice Knockout Liver Disease Wnt signaling pathway Hep G2 Cells Biological Sciences Cell biology Cytokine medicine.anatomical_structure Liver Hepatocyte Differentiation Tumor necrosis factor alpha Biotechnology 3D culture inflammatory cytokine injury Knockout organoid Biology liver General Biochemistry Genetics and Molecular Biology Article Cell Line 03 medical and health sciences Wnt Spheroids Cellular medicine Organoid Extracellular hepatocyte Human Umbilical Vein Endothelial Cells Animals Humans Antigens Cell Proliferation Tumor Necrosis Factor-alpha Regeneration (biology) RNA Antigens Differentiation 030104 developmental biology Transformed regeneration Hepatocytes Cellular Spheroids Digestive Diseases Developmental Biology |
| Zdroj: | Cell, vol 175, iss 6 |
| ISSN: | 1097-4172 |
| Popis: | In the healthy adult liver, most hepatocytes proliferate minimally. However, upon physical or chemical injury to the liver, hepatocytes proliferate extensively invivo under the direction of multiple extracellular cues, including Wnt and pro-inflammatory signals. Currently, liver organoids can be generated readily invitro from bile-duct epithelial cells, but nothepatocytes. 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 6months. Single-cell RNA sequencing reveals broad expression of hepatocyte markers. Strikingly, invitro-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. |
| Databáze: | OpenAIRE |
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