Controlled Expansion of Mammalian Cell Populations by Reversible Immortalization

Abstract

In 1996, reversible immortalization using SV40 large T antigens and the Cre/LoxP system was successfully achieved with primary human fibroblasts. The concept of reversible immortalization involves introducing an immortalizing agent, SV40 large T antigens, into primary cells, expanding the cells in the culture, and finally, efficiently removing the immortalizing agent using Cre/LoxP site-specific recombination. The resulting cell population is essentially identical to the initial primary cells, but greatly increased in number. Since this report, reversible immortalization has been realized with hepatocytes, pancreatic β-cells, hepatic stellate cells, endothelial cells, renal epithelial cells and myogenic cells. This method facilitates the study of cell transplantation as well as cell differentiation, the cell cycle and senescence, by allowing one to control cell proliferation.