Mesenchymal Stem Cell Treatment of Intervertebral Disc Lesion Prevents Fatty Infiltration and Fibrosis of the Multifidus Muscle, but not Cytokine and Muscle Fiber Changes

Gregory James, Linda Blomster, Leanne Hall, Annina B. Schmid, Cindy C. Shu, Christopher B. Little, James Melrose, Paul W. Hodges

Longitudinal case control animal model. To investigate effects of mesenchymal stem cell (MSC) treatment on multifidus muscle remodeling after intervertebral disc (IVD) lesion. Lesion and degeneration of IVDs causes structural remodeling of the multifidus muscle. Pro-inflammatory 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. 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 (CSA), and immunohistochemistry to study muscle fiber types. Real-time polymerase chain reactions quantified expression of TNF, IL-1β and TGF-β1. MSC-treatment of IVD lesion prevented the increased adipose and connective tissue CSA expected after IVD lesion. MSC-treatment did not prevent slow-to-fast muscle fiber type transformation. Gene expression of pro-inflammatory cytokines within the muscle was altered by the MSC-treatment of IVD. Increased IL-1β expression was prevented in the early treatment group and TNF and TGF-β1 expression was upregulated at 6 months. 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. 4.