Isolation of Variant Cell Lines During Serial Transplantation of Hematopoietic Cells Derived From Fetal Liver2

Abstract

Serial transplantation, in irradiated hosts, of cells derived from mouse fetal liver was found in some cases to result in a loss of proliferative capacity by the hematopoietic cells in the graft, as detected by a decrease in their ability to form colonies in the spleens of irradiated mice. In other cases, variant cell types emerged, which exhibited an unusually high efficiency of colony formation. Two such variant cell strains have been isolated, which differ from each other in colony-forming efficiency and in their sensitivity to γ-radiation. Some of the properties of these variant strains have been studied; both differ from normal hematopoietic cells and resemble lymphoma cells in that serial transplantation of the variant strains does not result in a decrease in proliferative capacity. In addition, the variant strains form splenic colonies showing no clear evidence of differentiation, and they are able to proliferate in the livers of irradiated adult hosts. They differ from lymphoma cells in that unirradiated, isologous animals receiving grafts of cells of the variant type do not form splenic colonies, nor have they been observed to develop malignant disease. Such unirradiated animals do, however, appear to develop a resistance to subsequent transplants of cells of the variant type. The properties of the variant cells are such that they have a selective advantage over normal hematopoietic cells in the irradiated, but not in the unirradiated, host.