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Clonal heterogeneity in murine liver myofibroblasts
A N Monteiro1, A T Geremias, R Borojevic
1Departamento de Bioquímica, Universidade Federal do Rio de Janeiro, Brasil.
Summary
Primary liver cells from Schistosoma mansoni-infected mice revealed distinct slow-growing and rapidly proliferating cell populations. Rapidly growing cells may fuel the slow-growing ones, potentially representing key cells in liver repair and fibrosis.
Area of Science:
- Immunology and Parasitology
- Cell Biology and Tissue Engineering
Background:
- Schistosoma mansoni infection induces hepatic granulomas in mice, serving as a source for primary liver cell cultures.
- Long-term culture of these primary cells (GR cells) led to the development of a continuous cell line (GRX) exhibiting a shift towards rapid proliferation.
Purpose of the Study:
- To analyze and compare the clonal heterogeneity of GR primary cells and the derived GRX continuous cell line.
- To investigate the potential roles of different cell clones in liver tissue repair and fibrotic reactions.
Main Methods:
- Isolation of GR primary cells from hepatic granulomas in C3H mice infected with Schistosoma mansoni.
- Derivation and long-term culture of the GRX continuous cell line from GR cells.
- Classification of cell clones based on substrate adherence, cell-cell adhesion (growth morphology), and fat droplet accumulation.
- Analysis of clonal proportions and stability in long-term cultures and after recloning.
Main Results:
- GR cells comprised two slow-growing clone types.
- GRX cells exhibited diverse phenotypes, including those present in GR cells, indicating broader clonal heterogeneity.
- The proportion of different clones in the GRX population remained stable during long-term culture and after recloning of rapidly proliferating cells.
Conclusions:
- A model is proposed where rapidly growing cells continuously contribute to the slow-growing cell population, maintaining it.
- Slow-growing clones may represent basal liver connective tissue cells involved in tissue repair.
- Highly proliferating clones, with extensive phenotype plasticity, could represent hypertrophic connective tissue cells implicated in liver fibrosis during chronic inflammation.