Stimulation of in vitro hematopoiesis by a murine fetal hepatocyte clone through cell—cell contact

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Abstract
We have previously shown that a fetal liver‐derived epithelial cell clone, FHC‐4D2, could support hematopoiesis in vitro through its colony‐stimulating factor (CSF) activities in a short‐term culture. In this study, since FHC‐4D2 cells were found capable of maintaining hematopoietic progenitors in the coculture for a long time, we examined how FHC‐4D2 could exert hematopoietic supporting activity in a long‐term culture by coculturing adult bone marrow (BM) cells or fetal liver (FL) cells on a monolayer of FHC‐4D2 cells. This clone could maintain the colony‐forming unit of granulocytes and macrophages (CFU‐GM) of BM for ≥ 12 weeks under the coculture condition, but the fibroblastic cell clone from the fetal liver, FHC‐4A3, could not support the survival of CFU‐GM, even for 1 week. In addition to BM CFU‐GM, the FHC‐4D2 clone also supported the survival of FL CFU‐GM, burst‐forming unit of erythroid cells (BFUe), and colony‐forming unit of mixed progenitors (CFU‐Mix) for longer than 4 weeks. When BM cells were separated by a membrane filter from the FHC‐4D2 cells in the coculture, the comparable number of CFU‐GM was maintained at day 3, but virtually no hematopoietic progenitors were detected at the end of the first week. CFU‐GM were present in both nonadherent and adherent cells to the FHC‐4D2 cells at day 3 of the coculture, but at day 7, the adherent population contained greater number of CFU‐GM. CFU‐GM derived from the adherent cells formed larger colonies and contained more bipotential CFU‐GM than the nonadherent population. When BM cells from mice given 5‐fluorouracil were cocultured with FHC‐4D2 cells under the limiting dilution condition, interleukin‐3 (IL‐3)‐responsive CFU‐GM were induced from immature hematopoietic progenitor cells that were otherwise unresponsive to IL‐3. From these data we conclude that the FHC‐4D2 clone could generate and maintain IL‐3‐responsive hematopoietic progenitors via close contact and that, in the fetal liver, the contact between hepatocytes and hematopoietic cells may be critically important in inducing the differentiation of resting, IL‐3‐unresponsive immature hematopoietic cells into CFU‐GM (progenitors responsive to IL‐3) and in triggering the self‐renewal of CFU‐GM.

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