Copyright ©The Author(s) 2020. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Stem Cells. Sep 26, 2020; 12(9): 938-951
Published online Sep 26, 2020. doi: 10.4252/wjsc.v12.i9.938
Role of the CXCR4-SDF1-HMGB1 pathway in the directional migration of cells and regeneration of affected organs
Nazmul Haque, Ismail M Fareez, Liew Fong Fong, Chanchal Mandal, Noor Hayaty Abu Kasim, Kranthi Raja Kacharaju, Pratiwi Soesilawati
Nazmul Haque, Ismail M Fareez, Liew Fong Fong, Department of Oral Biology and Biomedical Sciences, Faculty of Dentistry, MAHSA University, Selangor 42610, Malaysia
Chanchal Mandal, Biotechnology and Genetic Engineering Discipline, Life Science, Khulna University, Khulna 9208, Bangladesh
Noor Hayaty Abu Kasim, Faculty of Dentistry, University Kebangsaan Malaysia, Kuala Lumpur 50300, Malaysia
Noor Hayaty Abu Kasim, Faculty of Dental Medicine, Universitas Airlangga, Surabaya 411007, Indonesia
Kranthi Raja Kacharaju, Department of Conservative Dentistry, Faculty of Dentistry MAHSA University, Selangor 42610, Malaysia
Pratiwi Soesilawati, Department of Oral Biology, Faculty of Dental Medicine, Universitas Airlangga, Surabaya 60115, Indonesia
Author contributions: Fareez IM and Fong LF contributed equally to this work; Haque N contributed to the conception and design of the study; Mandel C, Kacharaju KR and Soesilawati P drafted and wrote the article; Haque N, Fareez IM, Fong LF and Abu Kasim NH contributed to the writing of the manuscript, made critical revisions related to relevant intellectual content of the manuscript; Haque N and Abu Kasim NH approved the final version of the article.
Supported by MAHSA University Grant, No. RP158-05/19.
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 NonCommercial (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: Nazmul Haque, PhD, Senior Lecturer, Department of Oral Biology and Biomedical Sciences, Faculty of Dentistry, MAHSA University, Jalan SP 2, Bandar Saujana Putra, Selangor 42610, Malaysia.;
Received: March 3, 2020
Peer-review started: March 3, 2020
First decision: June 7, 2020
Revised: June 18, 2020
Accepted: July 18, 2020
Article in press: July 18, 2020
Published online: September 26, 2020

In recent years, several studies have reported positive outcomes of cell-based therapies despite insufficient engraftment of transplanted cells. These findings have created a huge interest in the regenerative potential of paracrine factors released from transplanted stem or progenitor cells. Interestingly, this notion has also led scientists to question the role of proteins in the secretome produced by cells, tissues or organisms under certain conditions or at a particular time of regenerative therapy. Further studies have revealed that the secretomes derived from different cell types contain paracrine factors that could help to prevent apoptosis and induce proliferation of cells residing within the tissues of affected organs. This could also facilitate the migration of immune, progenitor and stem cells within the body to the site of inflammation. Of these different paracrine factors present within the secretome, researchers have given proper consideration to stromal cell-derived factor-1 (SDF1) that plays a vital role in tissue-specific migration of the cells needed for regeneration. Recently researchers recognized that SDF1 could facilitate site-specific migration of cells by regulating SDF1-CXCR4 and/or HMGB1-SDF1-CXCR4 pathways which is vital for tissue regeneration. Hence in this study, we have attempted to describe the role of different types of cells within the body in facilitating regeneration while emphasizing the HMGB1-SDF1-CXCR4 pathway that orchestrates the migration of cells to the site where regeneration is needed.

Keywords: C-X-C motif chemokine 12, Mesenchymal stem cells, Monocytes, Neutrophils, Peripheral blood mononuclear cells, Receptor for advanced glycation end products

Core tip: In the last few decades, cell-based regenerative therapy has received considerable attention for the treatment of degenerative diseases or the regeneration of injured organs. However, poor cell retention is considered a major drawback associated with the short-term regenerative benefits. Furthermore, the short-term regenerative benefits are linked to paracrine factors secreted by the transplanted stem cells. To improve regenerative outcomes, researchers have identified the role of stromal cell-derived factor-1 (SDF1) as a key chemotactic factor that can facilitate site-specific migration and retention of transplanted cells, and stem or progenitor cells within the body by activating the SDF1-CXCR4 or HMGB1-SFD1-CXCR4 pathways.