Copyright ©The Author(s) 2019. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Stem Cells. Oct 26, 2019; 11(10): 748-763
Published online Oct 26, 2019. doi: 10.4252/wjsc.v11.i10.748
Enhancing survival, engraftment, and osteogenic potential of mesenchymal stem cells
Daniel García-Sánchez, Darío Fernández, José C Rodríguez-Rey, Flor M Pérez-Campo
Daniel García-Sánchez, José C Rodríguez-Rey, Flor M Pérez-Campo, Department of Molecular Biology, Faculty of Medicine, University of Cantabria, Cantabria 39011, Spain
Darío Fernández, Laboratorio de Biología Celular y Molecular, Facultad de Odontología, Universidad Nacional del Nordeste, Corrientes W3400, Argentina
Darío Fernández, Consejo Nacional de Investigaciones científicas y Técnicas, Ciudad de Corrientes, Corrientes W3400, Argentina
Author contributions: All authors contributed to study conceptualization, original draft preparation, and manuscript editing.
Conflict-of-interest statement: None of the authors have any conflicts of interest relevant to this study.
Open-Access: 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:
Corresponding author: Flor M Pérez-Campo, BSc, PhD, Assistant Professor, Department of Molecular Biology, Faculty of Medicine, University of Cantabria, Avda. Cardenal Herrera Oria S/N, Cantabria 39011, Spain.
Telephone: +34-942-200958 Fax: +34-942-201945
Received: March 26, 2019
Peer-review started: March 28, 2019
First decision: June 17, 2019
Revised: July 15, 2019
Accepted: July 29, 2019
Article in press: July 29, 2019
Published online: October 26, 2019

Mesenchymal stem cells (MSCs) are promising candidates for bone regeneration therapies due to their plasticity and easiness of sourcing. MSC-based treatments are generally considered a safe procedure, however, the long-term results obtained up to now are far from satisfactory. The main causes of these therapeutic limitations are inefficient homing, engraftment, and osteogenic differentiation. Many studies have proposed modifications to improve MSC engraftment and osteogenic differentiation of the transplanted cells. Several strategies are aimed to improve cell resistance to the hostile microenvironment found in the recipient tissue and increase cell survival after transplantation. These strategies could range from a simple modification of the culture conditions, known as cell-preconditioning, to the genetic modification of the cells to avoid cellular senescence. Many efforts have also been done in order to enhance the osteogenic potential of the transplanted cells and induce bone formation, mainly by the use of bioactive or biomimetic scaffolds, although alternative approaches will also be discussed. This review aims to summarize several of the most recent approaches, providing an up-to-date view of the main developments in MSC-based regenerative techniques.

Keywords: Mesenchymal stem cells, Bone regeneration, Hypoxia, Anoikis, Preconditioning, Bioactive scaffolds, Senescence, Engraftment, Homing, Osteogenesis

Core tip: Mesenchymal stem cells (MSCs) are important tools for a wide range of therapeutic applications, including the treatment of critical size fractures or bone defects. However, whereas early clinical studies showed great expectations, long-term benefits of MSC-based treatments are not entirely successful. Transplanted cells had to face a series of important challenges that greatly reduce their survival and engraftment, and thus, their capacity to regenerate the target tissue. Although there is solid data indicating that the paracrine actions exerted by MSCs are equally important in the outcome of the treatment, this review is based on the current strategies aimed to enhance tissue regeneration directly occurring from the engraftment and differentiation of the transplanted MSCs.