Basic Study
Copyright ©The Author(s) 2019. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Stem Cells. Mar 26, 2019; 11(3): 196-211
Published online Mar 26, 2019. doi: 10.4252/wjsc.v11.i3.196
Stromal cell-derived factor-1α promotes recruitment and differentiation of nucleus pulposus-derived stem cells
Jin-Wei Ying, Tian-Yong Wen, Shi-Shen Pei, Ling-Hao Su, Di-Ke Ruan
Jin-Wei Ying, Shi-Shen Pei, Ling-Hao Su, Di-Ke Ruan, The Second School of Clinical Medicine, Southern Medical University, Guangzhou 510515, Guangdong Province, China
Jin-Wei Ying, Tian-Yong Wen, Shi-Shen Pei, Ling-Hao Su, Di-Ke Ruan, Department of Orthopedic Surgery, Navy General Hospital, Beijing 100048, China
Author contributions: Ying JW performed the majority of experiments and analyzed the data; Pei SS and Su LH performed the cell isolation and identification; Ying JW and Su LH performed the animal experiment; Wen TY collected the data and performed the statistical analysis; Ruan DK designed and coordinated the research; Ying JW and Ruan DK wrote the paper.
Supported by the National Natural Science Foundation of China, No. 81772399.
Institutional review board statement: The study was reviewed and approved by The General Hospital of the People’s Liberation Army Institutional Review Board.
Institutional animal care and use committee statement: All procedures involving animals were reviewed and approved by the Institutional Animal Care and Use Committee of The General Hospital of the People’s Liberation Army.
Conflict-of-interest statement: To the best of our knowledge, no conflict of interest exists.
ARRIVE guidelines statement: The authors have read the ARRIVE guidelines, and the manuscript was prepared and revised according to the ARRIVE guidelines.
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: Di-Ke Ruan, PhD, Chief Doctor, Doctor, Surgeon, the Second School of Clinical Medicine, Southern Medical University, South Shatai Road, Guangzhou 510515, Guangdong Province, China; Department of Orthopedic Surgery, Navy General Hospital, Fucheng Road, Beijing, China.
Telephone: +86-10-68780323 Fax: +86-10-68780323
Received: November 14, 2018
Peer-review started: November 15, 2018
First decision: December 10, 2018
Revised: December 19, 2018
Accepted: January 26, 2019
Article in press: January 26, 2019
Published online: March 26, 2019
Research background

Intervertebral disc (IVD) degeneration, the primary cause of low back pain, is an irreversible disease with no currently effective treatment. Nucleus pulposus-derived stem cells (NPSCs) with the capacity of multilineage differentiation have the regenerative potential to repair the degenerative IVD. Stromal cell-derived factor 1α (SDF-1α) released in the injury tissues displays a remarkable ability to attract stem cells for repairing tissues.

Research motivation

Mobilization and differentiation of NPSCs within the IVD represent an attractive target for future regenerative strategies for IVD degeneration in situ.

Research objectives

In the present study, the aim was to detect SDF-1α in the degenerative IVD and to determine its roles in the migration and differentiation of NPSCs.

Research methods

Enzyme-linked immunosorbent assay (ELISA), RT-qPCR, and immunohistochemistry were performed to demonstrate the levels of SDF-1α generated in the condition of IVD degeneration. The capacity of SDF-1α to recruit NPSCs was evaluated using wound healing and transwell migration assays. Western blot, RT-qPCR, and immunofluorescence were employed to determine the expression and location of C-X-C chemokine receptor type 4 (CXCR4) in response to SDF-1α. Cell micromass culture was used to assess the effect of SDF-1α on chondrogenic differentiation of NPSCs. Western blot, RT-qPCR, and histological analysis were conducted to examine the expression of chondrogenic markers such as aggrecan, collagen II, and Sox-9. CXCR4 antagonist AMD3100 was used to inhibit the effects of the SDF-1/CXCR4 axis on the migration and chondrogenic differentiation capacities of NPSCs.

Research results

SDF-1α was highly expressed in the inflammatory microenvironment of the degenerative IVD. SDF-1α promoted migration and chondrogenic differentiation of NPSCs in a dose-dependent manner. SDF-1α not only increased CXCR4 expression but also stimulated translocation of CXCR4 from the cytoplasm to membrane, accompanied by cytoskeletal rearrangement. Inhibition of the SDF-1/CXCR4 axis using CXCR4 antagonist AMD3100 effectively abolished the SDF-1α-induced migration and differentiation capacities of NPSCs.

Research conclusions

The present study demonstrated that the chemokine SDF-1α was pathogenically produced and secreted in the degenerative IVD, which plays a crucial role in promoting NPSC chondrogenic differentiation and migration toward injury sites via the SDF-1/CXCR4 axis.

Research perspectives

In summary, SDF-1α is highly released in the damaged or degenerative IVD and its receptor CXCR4 is expressed in the cytomembrane and cytoplasm of NPSCs. SDF-1α has the potential to enhance recruitment and chondrogenic differentiation of NPSCs via SDF-1/CXCR4 chemotaxis signals, which provides a novel insight into IVD regeneration mechanism and a promising therapeutic strategy to improve endogenous repair or regeneration of the degenerative IVD in situ. Future work will focus on understanding the possible downstream signaling pathways of the SDF-1/CXCR4 axis and their role in regulating the biological behaviors of NPSCs.