In vitro chemosensitivity study of human leukemic cells in a three-dimensional bone marrow culture system

Abstract

In the bone marrow, hematopoietic stem cell proliferation and differentiation are regulated by the hematopoietic microenvironment. This is reflected by the ability of the bone marrow microenvironment to alter the growth of leukemic cells, and protect leukemic cells from anti-cancer agents. Previously, we established a three-dimensional (3D) bone marrow culture system that maintained normal hematopoiesis, including prolongation of hematopoietic stem cell proliferation and differentiation. In the present study, we analyzed the effects of the anti-cancer drug, cytarabine, on the human leukemic cell line (K562) co-cultured with stromal cells in the 3D system. Comparisons were made with K562 cells treated with cytarabine in suspension or grown on a two-dimensional stromal cell monolayer (2D). We demonstrated that K562 cells cultured in the 3D system were more resistant to cytarabine treatment compared with cells grown in 2D or in suspension. Furthermore, there was a significant increase in the number of K562 cells in G0/G1 phase in 3D culture compared with cells grown in 2D or suspension cultures. These findings suggest that the differential response to cytarabine treatment in 3D culture may be related to the cell cycle period, which was modulated by stromal cells in the 3D microenvironment. Thus, the 3D culture system may be a valuable new tool for investigating leukemic cell-stromal cell interactions and the leukemic cell response to anti-cancer agents in vitro.