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bioRxiv · 10.1101/2023.01.03.522656

Evidence for in vitro extensive proliferation of adult hepatocytes and biliary epithelial cells

Katsuda, T.·Li, J.·Merrell, A. J.·Sussman, J.·Matsuzaki, J.·Ochiya, T.·Stanger, B. Z.
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Abstract

Over the last several years, a method has emerged which endows adult hepatocytes with in vitro proliferative capacity, producing chemically-induced liver progenitors (CLiPs). However, a recent study questioned the origin of these cells, suggesting that resident liver progenitor cells, but not hepatocytes, proliferate. Here, we provide lineage tracing-based evidence that adult hepatocytes acquire proliferative capacity in vitro. Unexpectedly, we also found that the CLiP method allows biliary epithelial cells to acquire extensive proliferative capacity. Interestingly, after long-term culture, hepatocyte-derived cells (hepCLiPs) and biliary-derived cells (bilCLiPs) become similar in their gene expression patterns, and they both exhibit differentiation capacity to form hepatocyte-like cells. Finally, we provide evidence that hepCLiPs can repopulate chronically injured mouse livers, reinforcing our earlier argument that CLiPs can be a cell source for liver regenerative medicine. Moreover, this study offers bilCLiPs as a potential cell source for liver regenerative medicine.

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Katsuda, T., Li, J., Merrell, A. J., Sussman, J., Matsuzaki, J., Ochiya, T., Stanger, B. Z.. 2023-01-03. Evidence for in vitro extensive proliferation of adult hepatocytes and biliary epithelial cells. https://doi.org/10.1101/2023.01.03.522656

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