Phenotypic and functional alterations of bone marrow MSCs exposed to multiple myeloma cells

Hye Joung Kim, So Young Eom, Saeyeon Hwang, Hyunsoo Kim, Jihee Won, Seok Chung, Seung Ah Yahng

Research output: Contribution to journalArticlepeer-review

Abstract

Backgrounds: The 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. Objective: In 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. Results: Co-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. Conclusion: Based 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.

Original languageEnglish
Pages (from-to)723-733
Number of pages11
JournalMolecular and Cellular Toxicology
Volume20
Issue number3
DOIs
Publication statusPublished - 2024 Jul

Bibliographical note

Publisher Copyright:
© The Author(s) under exclusive licence to The Korean Society of Toxicogenomics and Toxicoproteomics 2023.

Keywords

  • Co-culture
  • Differentiation
  • Mesenchymal stromal cell
  • Multiple myeloma
  • Tumor microenvironment

ASJC Scopus subject areas

  • Pathology and Forensic Medicine
  • Toxicology
  • General Pharmacology, Toxicology and Pharmaceutics
  • Public Health, Environmental and Occupational Health
  • Health, Toxicology and Mutagenesis

Fingerprint

Dive into the research topics of 'Phenotypic and functional alterations of bone marrow MSCs exposed to multiple myeloma cells'. Together they form a unique fingerprint.

Cite this