Clonal heterogeneity in murine liver myofibroblasts.

GR primary cells cultures were isolated from hepatic granulomas induced in C3H mice livers by Schistosoma mansoni infection; the GRX continuous cell line was derived from GR cells after long-term culture and a progressive drift towards a rapidly proliferating cell population. These cells were analyzed and compared in terms of their clonal heterogeneity. Clones were classified on the basis of cell substrate, cell-cell adhesion (growth morphology of the clone) and fat droplet accumulation. GR cells were composed of two slow-growing clone types, while GRX cells gave rise to clones with several phenotypes, including the two found in the GR cells. The overall proportion of different clones in the GRX cell population was stable in long-term cultures, as well as after recloning of the highly proliferating, but not the slowly proliferating, clones. We propose that the slow-growing clones are maintained in the overall population by continuous contribution of new slow-growing cells from the rapidly growing ones. The slow-growing clones may represent the basal population of liver connective tissue cells that can be mobilized into injured tissues and that are involved in tissue repair. The highly proliferating clones with a broad capacity of phenotype expression that arise after long-term growth stimulation of the local cell population may represent the hypertrophic connective tissue cells, such as those observed in progressive fibrotic reactions associated with chronic liver tissue inflammation.