Garcia-Gomez A, Sanchez-Guijo F, del Cañizo MC, San Miguel JF, Garayoa M. Multiple myeloma mesenchymal stromal cells: Contribution to myeloma bone disease and therapeutics. World J Stem Cells 2014; 6(3): 322-343 [PMID: 25126382 DOI: 10.4252/wjsc.v6.i3.322]
Corresponding Author of This Article
Mercedes Garayoa, PhD, Cancer Research Center, IBMCC (University of Salamanca-CSIC), Campus Miguel de Unamuno, Avda. Coimbra s/n, 37007 Salamanca, Spain. mgarayoa@usal.es
Research Domain of This Article
Hematology
Article-Type of This Article
Review
Open-Access Policy of This Article
This article is an open-access article which was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution Non Commercial (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: http://creativecommons.org/licenses/by-nc/4.0/
World J Stem Cells. Jul 26, 2014; 6(3): 322-343 Published online Jul 26, 2014. doi: 10.4252/wjsc.v6.i3.322
Multiple myeloma mesenchymal stromal cells: Contribution to myeloma bone disease and therapeutics
Antonio Garcia-Gomez, Fermin Sanchez-Guijo, M Consuelo del Cañizo, Jesus F San Miguel, Mercedes Garayoa
Antonio Garcia-Gomez, Fermin Sanchez-Guijo, Jesus F San Miguel, Mercedes Garayoa, Cancer Research Center, IBMCC (University of Salamanca-CSIC), 37007 Salamanca, Spain
Antonio Garcia-Gomez, Fermin Sanchez-Guijo, M Consuelo del Cañizo, Mercedes Garayoa, Jesús F San Miguel, Institute of Biomedical Research of Salamanca, University Hospital, 37007 Salamanca, Spain
Antonio Garcia-Gomez, Fermin Sanchez-Guijo, M Consuelo del Cañizo, Jesus F San Miguel, Mercedes Garayoa, Network of Centers for Regenerative Medicine and Cellular Therapy from Castilla y León, 37007 Salamanca, Spain
Fermin Sanchez-Guijo, M Consuelo del Cañizo, Spanish Cooperative Research Network in Cellular Therapy, 28029 Madrid, Spain
Jesus F San Miguel, Center for Applied Biomedical Research, Clinic University of Navarra, 31008 Pamplona, Spain
Author contributions: Garcia-Gomez A, Sanchez-Guijo F, del Cañizo MC and Garayoa M drafted and designed the manuscript; Garcia-Gomez A, Sanchez-Guijo F and Garayoa M summarized and wrote the manuscript; Garcia-Gomez A prepared the figures; Garcia-Gomez A and Sanchez-Guijo F prepared the tables; Garcia-Gomez A, Sanchez-Guijo F, del Cañizo MC, San Miguel JF and Garayoa M critically revised, edited and approved the manuscript.
Supported by Grants from the Spanish Ministry of Economía y Competitividad-Instituto de Salud Carlos III, No. PI12/02591; European Funds for Regional Development; the Spanish Health Thematic Networks of Cooperative Research in Cancer, No. RTICC RD12/0036/0058; Cellular Therapy, No. TerCel RD12/0019/0001, group 8; the Network of Centers for Regenerative Medicine and Cellular Therapy from Castilla y León; and the Spanish Society of Hematology and Hemotherapy (to Garcia-Gomez A)
Correspondence to: Mercedes Garayoa, PhD, Cancer Research Center, IBMCC (University of Salamanca-CSIC), Campus Miguel de Unamuno, Avda. Coimbra s/n, 37007 Salamanca, Spain. mgarayoa@usal.es
Telephone: +34-923-294812 Fax: +34-923-294743
Received: November 15, 2013 Revised: May 12, 2014 Accepted: June 10, 2014 Published online: July 26, 2014
Core Tip
Core tip: In multiple myeloma, bone marrow mesenchymal stromal cells (MSCs) primarily contribute to associated osteolytic lesions because of their defective differentiation to mature osteoblasts. Importantly, these MSCs also contribute to myeloma bone disease by enhancing osteoclast formation and activity through various mechanisms (i.e., increasing the receptor activator of nuclear factor-κB ligand/osteoprotegerin ratio, augmenting activin A secretion, uncoupling ephrinB2-EphB4 signaling and because of heightened production of Wnt5a). In addition, we overview signaling pathways involved in the osteogenic differentiation of MSCs or osteoblast activity and comment on the reported activity of bone-anabolic agents (preclinical or clinical stage) to restore bone homeostasis in myeloma patients.
