Review
Copyright ©The Author(s) 2015. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Stem Cells. Apr 26, 2015; 7(3): 630-640
Published online Apr 26, 2015. doi: 10.4252/wjsc.v7.i3.630
Recent advances in bone regeneration using adult stem cells
Hadar Zigdon-Giladi, Utai Rudich, Gal Michaeli Geller, Ayelet Evron
Hadar Zigdon-Giladi, Ayelet Evron, Department of Periodontology, School of Graduate Dentistry, Rambam Health Care Campus, Haifa 31096, Israel
Hadar Zigdon-Giladi, Ayelet Evron, Research Institute for Bone Repair, Rambam Health Care Campus, Haifa 31096, Israel
Hadar Zigdon-Giladi, Gal Michaeli Geller, the Rappaport Family Faculty of Medicine, Technion-Israel Institute of Technology, Haifa 31096, Israel
Utai Rudich, Orthopedic Department, Rambam Health Care Campus, Haifa 31096, Israel
Ayelet Evron, Evolutionary Developmental Biology, Faculty of Natural Sciences, Haifa University, Haifa 31096, Israel
Author contributions: Zigdon-Giladi H, Rudich U, Michaeli Geller G and Evron A designed and wrote this review paper.
Conflict-of-interest: The authors declare that they have no conflict of interest.
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: http://creativecommons.org/licenses/by-nc/4.0/
Correspondence to: Hadar Zigdon-Giladi, DMD, PhD, Research Institute for Bone Repair, Rambam Health Care Campus, P.O. Box 9602, Haifa 31096, Israel. hadar@tx.technion.ac.il
Telephone: +972-4-8543606 Fax: +972-4-8542467
Received: November 3, 2014
Peer-review started: November 4, 2014
First decision: November 27, 2014
Revised: December 30, 2014
Accepted: January 18, 2015
Article in press: January 20, 2015
Published online: April 26, 2015
Processing time: 170 Days and 14.1 Hours
Abstract

Bone is a highly vascularized tissue reliant on the close spatial and temporal association between blood vessels and bone cells. Therefore, cells that participate in vasculogenesis and osteogenesis play a pivotal role in bone formation during prenatal and postnatal periods. Nevertheless, spontaneous healing of bone fracture is occasionally impaired due to insufficient blood and cellular supply to the site of injury. In these cases, bone regeneration process is interrupted, which might result in delayed union or even nonunion of the fracture. Nonunion fracture is difficult to treat and have a high financial impact. In the last decade, numerous technological advancements in bone tissue engineering and cell-therapy opened new horizon in the field of bone regeneration. This review starts with presentation of the biological processes involved in bone development, bone remodeling, fracture healing process and the microenvironment at bone healing sites. Then, we discuss the rationale for using adult stem cells and listed the characteristics of the available cells for bone regeneration. The mechanism of action and epigenetic regulations for osteogenic differentiation are also described. Finally, we review the literature for translational and clinical trials that investigated the use of adult stem cells (mesenchymal stem cells, endothelial progenitor cells and CD34+ blood progenitors) for bone regeneration.

Keywords: Bone tissue; Mesenchymal stem cells; Tissue engineering; Osteogenesis; Angiogenesis; Endothelial progenitor cells

Core tip: Mesenchymal stem cells and blood derived progenitor cells have the potential to open new horizon for the treatment of bone defects. Numerous preclinical and clinical studies demonstrated angiogenic and osteogenic potential of these cells. Additional research is required in order to improve isolation and expansion techniques, as well as long term studies to follow the safety of this cellular approach.