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 sple en (colony-forming unit-spleen; CFU-S). The exact hierarchical level o f the hematopoietic progenitors which give rise to CFU-S is not fully established; however, cell populations highly enriched for repopulatin g stem cells appear to contain a high percentage of CFU-S. The experim ents reported here involved the injection of human fetal liver cells i nto mice, under conditions similar to those of the CFU-S test. These d ata 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 purificat ion of human fetal liver cells. When mice were injected with human fet al liver cells inactivated by irradiation, no human CFU-S were observe d. Positive staining of cells found in spleen colonies, using monoclon al antibodies specific for various human determinants, indicated the h uman origin of part of them. The presence of human cells within the co lonies was further confirmed by in situ hybridization using a probe sp ecific for human DNA. A mean of 30-40% of analyzed colonies was thus s hown to contain some patches of human cells. These data confirm that h uman hematopoietic cells are able to seed, proliferate, and differenti ate in a murine microenvironment.