Local RANTES/CCL5 Delivery and Peripheral Blood Mobilization of Endogenous Marrow-Derived Mesenchymal Stem Cells to Mitigate Lumbar Intervertebral Disc Degeneration
Recommended Citation
Gandhi S, Lai CS, Newton M, Hartner S, Fleischer M, Salisbury M, Gellci K, Park DK, Baker EA, and Baker KC. Local RANTES/CCL5 Delivery and Peripheral Blood Mobilization of Endogenous Marrow-Derived Mesenchymal Stem Cells to Mitigate Lumbar Intervertebral Disc Degeneration. Global Spine J 2025.
Document Type
Article
Publication Date
8-28-2025
Publication Title
Global Spine J
Abstract
Study Design: Translational rodent study.ObjectivesTo investigate (1) chemokine-mediated mesenchymal stem cell mobilization and homing to the intervertebral disc and (2) using this technique to mitigate intervertebral disc degeneration in a rat model.
Methods: (1) Recruitment of mesenchymal stem cells (MSCs) to intervertebral discs (IVD) was investigated using intradiscal chemokines. Hydrogel containing SDF-1, RANTES, MCP-1, or empty control was injected intradiscally, followed by near-infrared (NIR) imaging to observe MSC localization. (2) A rat IVD degeneration model was induced by annular puncture. Intradiscal RANTES injection and/or systemic AMD3100 injection was performed. Longitudinal imaging and histological analyses including Rutges Score (histologic degeneration) assessed IVD degeneration mitigation post-treatment up to 12-weeks. Statistical analyses included ANOVA and mixed-effects models to evaluate recruitment, retention, and regenerative potential of MSCs.
Results: (1) 24 rats were included in the investigation of MSC recruitment. In vivo NIR signal on 1-day post-intervention was highest with RANTES (P < .05). Ex vivo NIR signal at 14-days post-intervention was highest with RANTES (P < .05). (2) 36 IVD degeneration model rats underwent intradiscal RANTES and/or AMD3100 injection. AMD3100-treated groups showed larger nucleus pulposus (NP) volumes and reduced histologic damage, with lower Total Rutges scores (P = .004). RANTES treatment alone reduced Total Rutges scores (P = .009) and protected against IVD height loss at 6 weeks.
Conclusions: Intradiscal delivery of RANTES/CCL5 promotes a sustained and targeted recruitment of MSCs to the IVD. In a rat model of IVD degeneration, administration of systemic AMD3100 and intradiscal RANTES mitigates IVD degeneration.
PubMed ID
40876831
ePublication
ePub ahead of print
First Page
21925682251372917
Last Page
21925682251372917
