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Updated: Jun 29, 2025
Hepatic Progenitor Specification from Pluripotent Stem Cells using a Defined Differentiation System
Published on: May 10, 2020
Improvement in aged liver regeneration using cell transplantation with chemically induced liver progenitors
Kunihito Matsuguma1, Takanobu Hara1, Daisuke Miyamoto1
1Department of Surgery, Nagasaki University Graduate School of Biomedical Sciences, Nagasaki, Japan.
Background:
A decrease in the regenerative capacity of age-damaged liver tissue has been reported. Liver progenitor cells may play an important role in the regeneration of injured livers. In the present study we aimed to investigate improvements in the regenerative capacity of age-damaged livers using chemically induced liver progenitors (CLiPs) derived from mature hepatocytes.
Methods:
Old (>90 weeks) and young (<20 weeks) mice underwent 70% hepatectomy, with or without trans-splenic CLiP administration. The residual liver/bodyweight (LW/BW) ratio was measured on postoperative days 1 and 7, and changes in liver regeneration and histology were evaluated.
Results:
At 7 days post-hepatectomy, LW/BW ratios were significantly better in CLiP-treated old mice than in untreated old mice (p = .02). By contrast, no effect of CLiP transplantation was observed in young mice (p = .62). Immunofluorescence staining of liver tissue after CLiP administration showed an increase in Ki67-positive cells (p < .01). Flow cytometry analysis of green fluorescent protein-labeled CLiPs indicated that transplanted CLiPs differentiated into mature hepatocytes and were present in the recipient liver.
Conclusions:
CLiP transplantation appears to ameliorate the age-related decline in liver regeneration in mice.
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