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Copyright ©The Author(s) 2019. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Stem Cells. Sep 26, 2019; 11(9): 578-593
Published online Sep 26, 2019. doi: 10.4252/wjsc.v11.i9.578
Suitability and limitations of mesenchymal stem cells to elucidate human bone illness
Izaskun Mitxitorena, Arantza Infante, Blanca Gener, Clara I Rodríguez
Izaskun Mitxitorena, Arantza Infante, Blanca Gener, Clara I Rodríguez, Stem Cells and Cell Therapy Laboratory, Biocruces Bizkaia Health Research Institute, Cruces University Hospital, Barakaldo 48903, Bizkaia, Spain
Blanca Gener, Service of Genetics, Biocruces Bizkaia Health Research Institute, Cruces University Hospital, Barakaldo 48903, Bizkaia, Spain
Blanca Gener, Centre for Biomedical Network Research on Rare Diseases, Instituto de Salud Carlos III, Madrid 28005, Spain
Author contributions: Mitxitorena I and Infante A wrote the manuscript with support from Gener B and Rodríguez CI; Rodríguez CI supervised the manuscript.
Supported by Instituto de Salud Carlos III cofounded by ERDF/ESF, "A way to make Europe", No. PI15/00820 and PI18/00202; Basque Country government under the ELKARTEK program, No. kk-2018/00031/BC; Fundación Mutua Madrileña, No. AP165892017.
Conflict-of-interest statement: Dr. Rodríguez reports grants from ISCIII, grants from Basque Country government, and grants from Fundación Mutua Madrileña during the conduct of the study.
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 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/
Corresponding author: Clara I Rodríguez, PhD, Senior Scientist, Stem Cells and Cell Therapy Laboratory, BioCruces Bizkaia Health Research Institute, Cruces University Hospital, Plaza de Cruces S/N, Barakaldo 48903, Bizkaia, Spain. cirodriguez@osakidetza.eus
Telephone: +34-94-6006000
Received: February 28, 2019
Peer-review started: March 4, 2019
First decision: June 5, 2019
Revised: July 31, 2019
Accepted: August 27, 2019
Article in press: August 27, 2019
Published online: September 26, 2019
Abstract

Functional impairment of mesenchymal stem cells (MSCs), osteoblast progenitor cells, has been proposed to be a pathological mechanism contributing to bone disorders, such as osteoporosis (the most common bone disease) and other rare inherited skeletal dysplasias. Pathological bone loss can be caused not only by an enhanced bone resorption activity but also by hampered osteogenic differentiation of MSCs. The majority of the current treatment options counteract bone loss, and therefore bone fragility by blocking bone resorption. These so-called antiresorptive treatments, in spite of being effective at reducing fracture risk, cannot be administered for extended periods due to security concerns. Therefore, there is a real need to develop osteoanabolic therapies to promote bone formation. Human MSCs emerge as a suitable tool to study the etiology of bone disorders at the cellular level as well as to be used for cell therapy purposes for bone diseases. This review will focus on the most relevant findings using human MSCs as an in vitro cell model to unravel pathological bone mechanisms and the application and outcomes of human MSCs in cell therapy clinical trials for bone disease.

Keywords: Mesenchymal stem cells, Bone illness, Osteoporosis, Osteogenesis, Osteoanabolic therapies, In vitro cell models, Cell therapy

Core tip: Human mesenchymal stem cells (hMSCs) have emerged as an encouraging therapeutic strategy for the treatment of bone diseases. Moreover, certain limitations of animal models for the study of bone disorders highlight the suitability and benefits of hMSCs for the elucidation of these pathologies. The current review explains the available strategies based on hMSCs for bone illness, new treatment development, and future directions in the field for more accurate knowledge of the cause underlying these human pathologies.