Gregory James1, Linda Blomster1, Leanne Hall1, Annina B Schmid1,2, Cindy C Shu3, Christopher B Little3, James Melrose3,4, Paul W Hodges1. 1. Centre of Clinical Research Excellence in Spinal Pain, Injury & Health, School of Health and Rehabilitation Sciences, University of Queensland, Brisbane, Australia. 2. Nuffield Department of Clinical Neurosciences, Oxford University, United Kingdom. 3. Raymond Purves Bone and Joint Research Laboratories, Kolling Institute of Medical Research, Institute of Bone and Joint Research, The Royal North Shore Hospital, University of Sydney, St Leonards, NSW. 4. Graduate School of Biomedical Engineering, University of New South Wales, Sydney, Australia.
Abstract
STUDY DESIGN: Longitudinal case-control animal model. OBJECTIVE: To investigate effects of mesenchymal stem cell (MSC) treatment on multifidus muscle remodeling after intervertebral disc (IVD) lesion. SUMMARY OF BACKGROUND DATA: Lesion and degeneration of IVDs cause structural remodeling of the multifidus muscle. Proinflammatory cytokines are thought to contribute. MSC treatment restores IVD health after lesion but its effects on surrounding tissues remains unknown. Using an animal model of IVD degeneration, we assessed the effects of MSC treatment of IVDs on the structural remodeling and cytokine expression within the multifidus muscle. METHODS: An anterolateral lesion was performed on the L1-2, L3-4, and L5-6 IVDs in sheep. At either 4 (early treatment) or 12 (late treatment) weeks after IVD lesion, MSCs were injected into the lesioned IVD. Multifidus muscle was harvested from L2 (gene expression analysis) and L4 (histological analysis) at 3 or 6 months after IVD lesion and naïve controls for histological analysis of muscle, adipose, and connective tissue cross-sectional areas, and immunohistochemistry to study muscle fiber types. Real-time polymerase chain reactions quantified expression of tumor necrosis factor, interleukin-1β, and transforming growth factor-β1. RESULTS: MSC treatment of IVD lesion prevented the increased adipose and connective tissue cross-sectional area expected after IVD lesion. MSC treatment did not prevent slow-to-fast muscle fiber type transformation. Gene expression of proinflammatory cytokines within the muscle was altered by the MSC treatment of IVD. Increased interleukin-1β expression was prevented in the early treatment group and tumor necrosis factor and transforming growth factor-β1 expression was upregulated at 6 months. CONCLUSION: Results show that although MSC treatment prevents fatty infiltration and fibrosis of the multifidus muscle after IVD lesion, it cannot prevent a muscle inflammatory response and muscle fiber transformation. These findings highlight the potential role of MSC therapy after IVD injury, but reveals that other interventions may also be necessary to optimize recovery of muscle. LEVEL OF EVIDENCE: 4.
STUDY DESIGN: Longitudinal case-control animal model. OBJECTIVE: To investigate effects of mesenchymal stem cell (MSC) treatment on multifidus muscle remodeling after intervertebral disc (IVD) lesion. SUMMARY OF BACKGROUND DATA: Lesion and degeneration of IVDs cause structural remodeling of the multifidus muscle. Proinflammatory cytokines are thought to contribute. MSC treatment restores IVD health after lesion but its effects on surrounding tissues remains unknown. Using an animal model of IVD degeneration, we assessed the effects of MSC treatment of IVDs on the structural remodeling and cytokine expression within the multifidus muscle. METHODS: An anterolateral lesion was performed on the L1-2, L3-4, and L5-6 IVDs in sheep. At either 4 (early treatment) or 12 (late treatment) weeks after IVD lesion, MSCs were injected into the lesioned IVD. Multifidus muscle was harvested from L2 (gene expression analysis) and L4 (histological analysis) at 3 or 6 months after IVD lesion and naïve controls for histological analysis of muscle, adipose, and connective tissue cross-sectional areas, and immunohistochemistry to study muscle fiber types. Real-time polymerase chain reactions quantified expression of tumor necrosis factor, interleukin-1β, and transforming growth factor-β1. RESULTS: MSC treatment of IVD lesion prevented the increased adipose and connective tissue cross-sectional area expected after IVD lesion. MSC treatment did not prevent slow-to-fast muscle fiber type transformation. Gene expression of proinflammatory cytokines within the muscle was altered by the MSC treatment of IVD. Increased interleukin-1β expression was prevented in the early treatment group and tumor necrosis factor and transforming growth factor-β1 expression was upregulated at 6 months. CONCLUSION: Results show that although MSC treatment prevents fatty infiltration and fibrosis of the multifidus muscle after IVD lesion, it cannot prevent a muscle inflammatory response and muscle fiber transformation. These findings highlight the potential role of MSC therapy after IVD injury, but reveals that other interventions may also be necessary to optimize recovery of muscle. LEVEL OF EVIDENCE: 4.
Authors: Gregory James; Kathleen A Sluka; Linda Blomster; Leanne Hall; Annina B Schmid; Cindy C Shu; Christopher B Little; James Melrose; Paul W Hodges Journal: Eur Spine J Date: 2018-06-12 Impact factor: 3.134
Authors: Gregory James; Carla Stecco; Linda Blomster; Leanne Hall; Annina B Schmid; Cindy C Shu; Christopher B Little; James Melrose; Paul W Hodges Journal: Eur Spine J Date: 2022-05-27 Impact factor: 2.721
Authors: Cindy C Shu; Andrew Dart; Robin Bell; Christina Dart; Elizabeth Clarke; Margaret M Smith; Christopher B Little; James Melrose Journal: JOR Spine Date: 2018-10-10