Kinetics of MM1.S Multiple Myeloma Cells in a 3D Polymer Particle Culture System with Bone Marrow Stromal Cells and Bortezomib

TL;DR

This study examines how different bone marrow stromal cells affect the growth of multiple myeloma cells in a 3D culture system and their response to bortezomib.

Contribution

The study reveals distinct effects of MS-5 and Tst-4 stromal cells on MM1.S cell growth and drug resistance in a 3D culture system.

Findings

MM1.S cells grew slower in 3D culture with MS-5 stromal cells compared to 2D and Tst-4 3D cultures.

MS-5 stromal cells protected MM1.S cells from bortezomib's cytocidal effects in 3D culture.

Stromal cell type significantly influences MM1.S cell kinetics in 3D systems.

Abstract

Background: Three-dimensional (3D) culture systems use polymer particles with a bone marrow stroma cell feeder layer to reproduce a biostructural hematopoiesis state more effectively than in conventional two-dimensional (2D) culture methods. The 3D culture maintains normal hematopoiesis, resulting in prolongation of hematopoietic stem cell proliferation and differentiation, while the bone marrow stromal cells in the culture alter the growth of leukemic cells and protect them from anticancer agents. However, the effect of stromal cells on hematopoietic stem cell proliferation and differentiation and neoplastic cells, including leukemia, in 3D culture is still a point of contention. Methods: We assessed the mechanism of two different bone-marrow-derived stromal cells (i.e., MS-5 and Tst-4) with different characteristics by using a feeder layer in the 3D culture to compare their supportive action on leukemic cells, focusing on the role of 3D cultures constructed with bone marrow stromal cells in leukemic cell growth. Multiple myeloma cells are strongly related to stromal cells in their proliferation; hence, cloned MM1.S cells derived from multiple myeloma were cocultured in 3D, and their cell growth was examined. We also examined the effect of the antineoplastic agent bortezomib, 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 3D conditions, cell growth was found to be slow compared with that in 2D culture, as well as with those in both the 2D and 3D cocultures with Tst-4 stroma. Additionally, the MS-5 cells in the 3D culture protected the MM1.S cells from the cytocidal effect of the bortezomib treatment. Different MM1.S cell kinetics were observed depending on the stromal cells used, suggesting their inherent and complicated characteristics.

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