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

Intervertebral disc (IVD) degeneration is a condition characterized by a reduction in the water and extracellular matrix content of the nucleus pulposus (NP) and is considered as one of the dominating contributing factors to low back pain. Recent evidence suggests that stromal cell-derived factor 1α (SDF-1α) and its receptor C-X-C chemokine receptor type 4 (CXCR4) direct the migration of stem cells associated with injury repair in different musculoskeletal tissues.


To investigate the effects of SDF-1α on recruitment and chondrogenic differentiation of nucleus pulposus-derived stem cells (NPSCs).


We performed real-time RT-PCR and enzyme-linked immunosorbent assay to examine the expression of SDF-1α in nucleus pulposus cells after treatment with pro-inflammatory cytokines in vitro. An animal model of IVD degeneration was established using annular fibrosus puncture in rat coccygeal discs. Tissue samples were collected from normal control and degeneration groups. Differences in the expression of SDF-1α between the normal and degenerative IVDs were analyzed by immunohistochemistry. The migration capacity of NPSCs induced by SDF-1α was evaluated using wound healing and transwell migration assays. To determine the effect of SDF-1α on chondrogenic differentiation of NPSCs, we conducted cell micromass culture and examined the expression levels of Sox-9, aggrecan, and collagen II. Moreover, the roles of SDF-1/CXCR4 axis in the migration and chondrogenesis differentiation of NPSCs were analyzed by immunofluorescence, immunoblotting, and real-time RT-PCR.


SDF-1α was significantly upregulated in the native IVD cells cultured in vitro with pro-inflammatory cytokines, such as interleukin-1β and tumor necrosis factor-α, mimicking the degenerative settings. Immunohistochemical staining showed that the level of SDF-1α was also significantly higher in the degenerative group than in the normal group. SDF-1α enhanced the migration capacity of NPSCs in a dose-dependent manner. In addition, SDF-1α induced chondrogenic differentiation of NPSCs, as evidenced by the increased expression of chondrogenic markers using histological and immunoblotting analyses. Real-time RT-PCR, immunoblotting, and immunofluorescence showed that SDF-1α not only increased CXCR4 expression but also stimulated translocation of CXCR4 from the cytoplasm to membrane, accompanied by cytoskeletal rearrangement. Furthermore, blocking CXCR4 with AMD3100 effectively suppressed the SDF-1α-induced migration and differentiation capacities of NPSCs.


These findings demonstrate that SDF-1α has the potential to enhance recruitment and chondrogenic differentiation of NPSCs via SDF-1/CXCR4 chemotaxis signals that contribute to IVD regeneration.

Keywords: Stromal cell-derived factor 1α, CXC chemokine receptor 4, Nucleus pulposus-derived stem cells, Intervertebral disc degeneration, Endogenous regeneration

Core tip: The chemokine stromal cell-derived factor-1α (SDF-1α) is upregulated in the pro-inflammatory microenvironment or degenerative intervertebral disc (IVD). The present study demonstrates for the first time that SDF-1α effectively promotes migration and chondrogenic differentiation of nucleus pulposus-derived stem cells (NPSCs), which serve as endogenous progenitor/stem cells residing in the IVD. In addition, SDF-1/CXCR4 chemotaxis signals may play a crucial role in the process of recruitment and chondrogenic differentiation of NPSCs that are involved in spontaneous IVD regeneration in the early stage of IVD degeneration.