Copyright ©The Author(s) 2019. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Stem Cells. Aug 26, 2019; 11(8): 464-475
Published online Aug 26, 2019. doi: 10.4252/wjsc.v11.i8.464
Orchestrating stem cell fate: Novel tools for regenerative medicine
Sara Cruciani, Sara Santaniello, Andrea Montella, Carlo Ventura, Margherita Maioli
Sara Cruciani, Sara Santaniello, Andrea Montella, Margherita Maioli, Department of Biomedical Sciences, University of Sassari, Sassari 07100, Italy
Sara Cruciani, Sara Santaniello, Carlo Ventura, Margherita Maioli, Laboratory of Molecular Biology and Stem Cell Engineering, National Institute of Biostructures and Biosystems – Eldor Lab, Innovation Accelerator, Consiglio Nazionale delle Ricerche, Bologna 40129, Italy
Andrea Montella, Operative Unit of Clinical Genetics and Developmental Biology, Sassari 07100, Italy
Margherita Maioli, Istituto di Ricerca Genetica e Biomedica, Consiglio Nazionale delle Ricerche, Cagliari 09042, Italy
Margherita Maioli, Center for Developmental Biology and Reprogramming-CEDEBIOR, Department of Biomedical Sciences, University of Sassari, Sassari 07100, Italy
Author contributions: All authors contributed in the design and writing of the paper, literature review and the analysis, revision and approval of the final version.
Conflict-of-interest statement: The authors declare no conflicts of interest.
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:
Corresponding author: Margherita Maioli, PhD, Professor, Department of Biomedical Sciences, University of Sassari, Viale San Pietro 43/B, Sassari 07100, Italy.
Telephone: +39-07-9228277
Received: February 20, 2019
Peer-review started: February 20, 2019
First decision: April 15, 2019
Revised: May 28, 2019
Accepted: June 12, 2019
Article in press: June 12, 2019
Published online: August 26, 2019

Mesenchymal stem cells are undifferentiated cells able to acquire different phenotypes under specific stimuli. In vitro manipulation of these cells is focused on understanding stem cell behavior, proliferation and pluripotency. Latest advances in the field of stem cells concern epigenetics and its role in maintaining self-renewal and differentiation capabilities. Chemical and physical stimuli can modulate cell commitment, acting on gene expression of Oct-4, Sox-2 and Nanog, the main stemness markers, and tissue-lineage specific genes. This activation or repression is related to the activity of chromatin-remodeling factors and epigenetic regulators, new targets of many cell therapies. The aim of this review is to afford a view of the current state of in vitro and in vivo stem cell applications, highlighting the strategies used to influence stem cell commitment for current and future cell therapies. Identifying the molecular mechanisms controlling stem cell fate could open up novel strategies for tissue repairing processes and other clinical applications.

Keywords: Stem cells, Epigenetics, Self-renewal, In vitro differentiation, Physical stimuli, Stem cell fate, Clinical practice, Cell transplantation

Core tip: The latest advances in the field of stem cells concern epigenetics and its role in self-renewal and differentiation capability. Activation or silencing of genes controlling stemness and tissue-lineage specification are related to chromatin-remodeling factors and epigenetic regulators. In this review, we focused on the principal epigenetic markers that regulate stem cell pluripotency, in vitro manipulation and the current state-of-the-art in vivo applications of human mesenchymal stem cells.