Effects of Stromal Cell-Derived Factor-1α Secreted in Degenerative Intervertebral Disc on Activation and Recruitment of Nucleus Pulposus-Derived Stem Cells

Stromal cell-derived factor-1α (SDF-1α) plays a significant role in mobilizing and recruiting mesenchymal stem cells (MSCs) to the sites of injury. This study investigated the potential of SDF-1α released in the degenerative intervertebral disc (IVD) to activate and recruit endogenous nucleus pulposus-derived stem cells (NPSCs) for regeneration in situ. We found SDF-1α was highly expressed and secreted by the native disc cells when cultured in the proinflammatory mediators in vitro mimicking the degenerative settings. Immunohistochemical staining also showed that the expression level of SDF-1α was significantly higher in the degenerative group compared to that in the normal group. In addition to enhancement of viability, SDF-1α significantly increased the number of NPSCs migrating into the center of the nucleotomized bovine IVD ex vivo. After the systemic delivery of exogenous PKH26-labelled NPSCs into the rats in vivo, there was a significant difference in the distribution of the migrated cells between the normal and the degenerative IVDs, which might be caused by the different expression levels of SDF-1α. However, blocking CXC chemokine receptor 4 (CXCR4) with AMD3100 effectively abrogated SDF-1α-stimulated proliferation and migration. Taken together, SDF-1α may be a key chemoattractant that is highly produced in response to the degenerative changes, which can be used to enhance the proliferation and recruitment of endogenous stem cells into the IVDs. These findings may be of importance for understanding IVD regenerative mechanisms and development of regenerative strategies in situ for IVD degeneration.

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In Situ Osteochondral Regeneration by Controlled Release of Stromal Cell-Derived Factor-1 Chemokine from Injectable Biomaterials: A Preclinical Evaluation in Animal Model

Journal of Biomaterials and Tissue Engineering ◽

10.1166/jbt.2019.2096 ◽

2019 ◽

Vol 9 (7) ◽

pp. 958-967

Author(s):

Huali Chen ◽

Dengwei He ◽

Ye Zhu ◽

Weiyang Yu ◽

Murugan Ramalingam ◽

...

Keyword(s):

Stem Cells ◽

Stromal Cell ◽

Gelation Time ◽

Osteochondral Repair ◽

Model Animal ◽

Osteochondral Tissue ◽

Stromal Cell Derived Factor ◽

Potential Strategy ◽

New Formulation

Osteochondral defect (OD) refers to damage in the area of articular cartilage extended to the subchondral bone, affecting millions of people worldwide. In situ osteochondral tissue engineering approach, which aims to activate the body's native stem cells and recruit them to the defective site by utilizing biomaterials, has become a potential strategy for repairing focal chondral lesions. However, due to the lack of cell-instructive potential, most of the biomaterials fail to recruit stem cells from the host environment and trigger the cellular and molecular functions necessary for tissue regeneration. In this study, the authors report a new formulation of injectable biomaterial system, based on stromal cell-derived factor-1 (SDF-1)-encapsulated poly(lactic-co-glycolic acid) (PLGA) microspheres loaded chitosan-gelatin (CS-GEL) composite hydrogel system (SDF-1/CS-GEL@PLGA), with the aim of imparting in situ cell-instructive and osteochondral tissue regenerative potential. The osteochondral regenerative potential of SDF-1/CS-GEL@PLGA was studied in rabbit as a model animal and the results were compared with the CS-GEL@PLGA without the SDF-1. The results of this study showed that the CS-GEL@PLGA hydrogel had better gelation time and longer release cycle (>30 days) than the CS-GEL. In addition, SDF-1/CS-GEL@PLGA hydrogels promoted the repair of osteochondral defects in rabbits within 12 weeks as compared to the CS-GEL@PLGA hydrogels. Therefore, based on the experimental data, SDF-1/CS-GEL@PLGA hydrogel is a promising injectable biomaterial system for osteochondral repair and regeneration.

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