Kim, Hye Joung Eom, So Young Hwang, Saeyeon Kim, Hyunsoo Won, Jihee Chung, Seok Yahng, Seung-Ah 2024-01-19T08:02:23Z 2024-01-19T08:02:23Z 2024-01-04 2024-07 1738-642X https://pubs.kist.re.kr/handle/201004/113014 BackgroundsThe direct and indirect interactions between multiple myeloma (MM) cells and bone marrow mesenchymal stromal cells (MSCs) play crucial roles in the formation of the bone marrow environment, disease progression, and drug resistance development. However, it remains unclear how MM cells and MSCs individually influence each other to induce these phenomena.ObjectiveIn this study, we focused on observing changes in MSCs induced by MM cells. Changes in MSCs due to exposure to MM cells were observed by assessing cell proliferation, apoptosis, cell cycle, and morphology. Furthermore, the unique abilities of MSCs were confirmed through differentiation potential and MSC marker expression, along with the demonstration of senescence. Gene profiling was performed to elucidate the mechanisms underlying these changes.ResultsCo-culturing MM cells with MSCs did not alter the morphology or proliferation of MSCs but increased apoptosis. As apoptosis increased, damaged deoxyribonucleic acid (DNA) was repaired, leading to the activation of the cell cycle with an increase in the S phase, resulting in no significant changes in cell proliferation and morphology. Osteogenesis and adipogenesis generally decreased by co-culturing with MM cells, and senescence increased. Significant differences were observed in the expression of MSC marker genes. Gene profiling revealed changes in gene expression following osteogenic differentiation.ConclusionBased on these results, MSCs exposed to MM cells exhibited an increase in the S phase of the cell cycle, leading to the recovery of cells undergoing apoptosis. Osteogenesis and adipogenesis decreased, whereas senescence increased, suggesting that these changes were attributed to the overall MSC characteristics and genetic mechanisms. English 대한독성 유전단백체 학회 Phenotypic and functional alterations of bone marrow MSCs exposed to multiple myeloma cells Article 10.1007/s13273-023-00415-5 1 Molecular & Cellular Toxicology, v.20, no.3, pp.723 - 733 Molecular & Cellular Toxicology 20 3 723 733 N scie scopus kci 001125885600001 2-s2.0-85179999952 Biochemistry & Molecular Biology Toxicology Biochemistry & Molecular Biology Toxicology Article MESENCHYMAL STEM-CELLS TRANSPLANTATION ABNORMALITIES LENALIDOMIDE Tumor microenvironment Co-culture Differentiation Multiple myeloma Mesenchymal stromal cell