Human fetal liver cells induce colonies in spleen of lethally irradiated mice.

Murine hematopoietic tissues contain cells which, upon injection into lethally irradiated mice, produce nodules on the surface of their spleen (colony-forming unit--spleen; CFU-S). The exact hierarchical level of the hematopoietic progenitors which give rise to CFU-S is not fully established; however, cell populations highly enriched for repopulating stem cells appear to contain a high percentage of CFU-S. The experiments reported here involved the injection of human fetal liver cells into mice, under conditions similar to those of the CFU-S test. These data demonstrate that human fetal liver cells are able to induce spleen colonies (tentatively called human CFU-S) when injected into lethally irradiated mice. The number of CFU-S was increased by prior purification of human fetal liver cells. When mice were injected with human fetal liver cells inactivated by irradiation, no human CFU-S were observed. Positive staining of cells found in spleen colonies, using monoclonal antibodies specific for various human determinants, indicated the human origin of part of them. The presence of human cells within the colonies was further confirmed by in situ hybridization using a probe specific for human DNA. A mean of 30-40% of analyzed colonies was thus shown to contain some patches of human cells. These data confirm that human hematopoietic cells are able to seed, proliferate, and differentiate in a murine microenvironment.