333 Intervertebral Disc Repair Following Microdiscectomy Mediated by Pentosan Polysulfate Primed Mesenchymal Progenitor Cells in an Ovine Model

Abstract

Abstract INTRODUCTION Lumbar microdiscectomy treats neural compression but fails to halt disc degeneration. Consequently, 10 20% of patients develop debilitating back pain and approximately 15% undergo further surgical intervention. In-vitro pre-incubation of mesenchymal precursor cells (MPCs) with pentosan polysulfate (PPS), enhances viability and chondrogenic differentiation, but inhibits osteogenesis. This study investigated the potential of PPS primed mesenchymal precursor cells (pMPCs) in a gelatin scaffold to facilitate disc repair in an ovine model. METHODS Eighteen adult ewes underwent pre-operative 3T MRI followed by lumbar microdiscectomy at two levels. Sheep were randomized into three groups. The injured control (IC) group received no further treatment; the MPC group were implanted with non-primed MPC + scaffold; the pMPC group received the pMPC + scaffold. Necropsies were performed at six months. Analysis consisted of 3T and 9.4T MRI, gross morphological, histological and biochemical analysis for proteoglycans, collagen and DNA content. RESULTS >MPC and pMPC discs demonstrated significantly reduced disc height loss (P < 0.05) and reduced Pfirrmann grades (P < 0.001) relative to IC discs. pMPC disc segments were significantly less degenerate than IC discs on gross morphology. Proteoglycan content of pMPC discs was significantly greater than IC discs and not significantly different to controls for the injured annulus fibrosus (AF) region and nucleus pulposus (NP) region contralateral to the injury. DNA content for pMPC discs was significantly less than IC discs for the NP & AF injury and adjacent regions. Histological analysis demonstrated increased organization and decreased degeneration in pMPC discs while MPC discs displayed increased vascular infiltration. CONCLUSION pMPCs post microdiscectomy reduced disc degeneration, improved disc height and matrix organization, NP proteoglycan content and histological degeneration relative to microdiscectomy alone. This suggests a potential therapeutic application of pMPCs in promoting disc repair and reducing the incidence of low back pain and further surgery following microdiscectomy.