Copyright ©The Author(s) 2023. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Stem Cells. May 26, 2023; 15(5): 421-437
Published online May 26, 2023. doi: 10.4252/wjsc.v15.i5.421
Communication between bone marrow mesenchymal stem cells and multiple myeloma cells: Impact on disease progression
Daniel García-Sánchez, Alberto González-González, Ana Alfonso-Fernández, Mónica Del Dujo-Gutiérrez, Flor M Pérez-Campo
Daniel García-Sánchez, Alberto González-González, Mónica Del Dujo-Gutiérrez, Flor M Pérez-Campo, Department of Molecular Biology_IDIVAL, Faculty of Medicine, University of Cantabria, Santander 39011, Cantabria, Spain
Ana Alfonso-Fernández, Servicio de Traumatología y Cirugía Ortopédica, Hospital Universitario Marqués de Valdecilla, Instituto de Investigación Sanitaria Valdecilla (IDIVAL), Facultad de Medicina, Universidad de Cantabria, Santander 39008, Cantabria, Spain
Author contributions: All authors contributed to study conceptualization, original draft preparation, and manuscript editing.
Supported by The “Instituto de Salud Carlos III, No. PI22/00264; A Predoctoral Program in Biomedicine from The University of Cantabria and The Instituto de Investigación Valdecilla-IDIVAL (Alberto González-González and Daniel García-Sánchez), No. PREVAL19/02, and No. PREVAL20/01; “Investigo Program”, part of the “Plan Nacional de Recuperación, Transformación y Resiliencia” from The Spanish Government (Mónica del Dujo-Gutiérrez).
Conflict-of-interest statement: A grant from The “Instituto de Salud Carlos III, No. PI22/00264; Alberto González-González and Daniel García-Sánchez are both supported by a predoctoral program in Biomedicine from the University of Cantabria and the Instituto de Investigación Valdecilla -IDIVAL (PREVAL 19/02 and PREVAL 20/01). Mónica del Dujo-Gutiérrez is suported by the “Investigo Program”, part of the “Plan Nacional de Recuperación, Transformación y Resiliencia” from the Spanish Government.
Open-Access: This article is an open-access article that was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution NonCommercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See:
Corresponding author: Flor M Pérez-Campo, MSc, PhD, Assistant Professor, Senior Scientist, Department of Molecular Biology_IDIVAL, Faculty of Medicine, University of Cantabria, Avda Cardenal Herrera Oria S/N, Santander 39011, Cantabria, Spain.
Received: January 29, 2023
Peer-review started: January 29, 2023
First decision: February 13, 2023
Revised: February 27, 2023
Accepted: April 17, 2023
Article in press: April 17, 2023
Published online: May 26, 2023

Multiple myeloma (MM) is a hematological malignancy characterized by the accumulation of immunoglobulin-secreting clonal plasma cells at the bone marrow (BM). The interaction between MM cells and the BM microenvironment, and specifically BM mesenchymal stem cells (BM-MSCs), has a key role in the pathophysiology of this disease. Multiple data support the idea that BM-MSCs not only enhance the proliferation and survival of MM cells but are also involved in the resistance of MM cells to certain drugs, aiding the progression of this hematological tumor. The relation of MM cells with the resident BM-MSCs is a two-way interaction. MM modulate the behavior of BM-MSCs altering their expression profile, proliferation rate, osteogenic potential, and expression of senescence markers. In turn, modified BM-MSCs can produce a set of cytokines that would modulate the BM microenvironment to favor disease progression. The interaction between MM cells and BM-MSCs can be mediated by the secretion of a variety of soluble factors and extracellular vesicles carrying microRNAs, long non-coding RNAs or other molecules. However, the communication between these two types of cells could also involve a direct physical interaction through adhesion molecules or tunneling nanotubes. Thus, understanding the way this communication works and developing strategies to interfere in the process, would preclude the expansion of the MM cells and might offer alternative treatments for this incurable disease.

Keywords: Multiple myeloma, Mesenchymal stem cells, Bone marrow microenvironment, Soluble factors, Extra-cellular vesicles, Cells adhesion molecules, Tunnelling-nanotubes

Core Tip: Mesenchymal stem cells (MSCs), the main cell population of the bone marrow (BM) stroma, can influence BM microenvironment through their paracrine activity, involving both soluble factors and extracellular vesicles, but also through direct communication. Being the BM the predominant localization of multiple myeloma cells (MM), finding the appropriate conditions at this niche, is key for the survival and expansion of tumour cells and thus, for the progression of the disease. Since the activity of BM-MSCs could determine the fate of MM cells at BM, these cells could be interesting targets for the design of new antitumor drugs.