Kinetics of Multiple Myeloma Derived Cloned MM1.S Cells in the Three-Dimensional Culture System Constructed by Polymer Particles and Bone Marrow Stromal Cells in the Presence of Proteasome Inhibitor, Bortezomib

Background: The three-dimensional (3D) culture system that uses polymer particles with a bone marrow stroma cell feeder layer reproduces a biostructural hematopoiesis state effectively as compared to the conventional two-dimensional (2D) culture method. The 3D culture that maintains normal hematopoiesis, including prolongation of the hematopoietic stem cell proliferation and differentiation. The bone marrow stromal cells in a 3D culture, alter leukemic cell growth and protect the leukemic cells from anticancer agents. However, the mechanism of stromal cells on the hematopoietic stem cell proliferation and differentiation and neoplastic cells, including leukemia in the 3D culture, still bear many questions. Methods: We assessed the mechanism of two different bone marrow-derived stromal cells (i.e., MS-5 and Tst-4) bearing different characteristics, by using for a feeder layer in the 3D culture to compare the supportive action to leukemic cells. We focused on the role of the 3D culture constructed with the bone marrow stromal cells on the leukemic cell growth. Multiple myeloma cells are strongly related to the stromal cells in their proliferation; hence, the cloned MM1.S cells derived from multiple myeloma were cocultured in the 3D, and their cell growth was examined. We also examined the effect of the antineoplastic agent, bortezomib, which is a proteasome inhibitor, in the 3D culture system with a different stromal cell feeder. Results and conclusions: When MM1.S myeloma cells were cultured with MS-5 stroma in a 3D condition, the cell growth was found to be slow compared with that in the 2D culture and also with those in both the 2D and 3D cocultures with Tst-4 stroma. The MS-5 cells in the 3D culture protected the MM1.S cells from the cytocidal effect of the bortezomib treatment. Different kinetics of the MM1.S cells were observed depending on the stromal cells, suggesting their inherent and complicated characteristic.