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Degeneration of the intervertebral disc (IVD) results in deterioration of the spinal motion segment and can lead to debilitating back pain. Given the established mitotic and anti-apoptotic effects of recombinant human platelet-derived growth factor-BB (rhPDGF-BB) in a variety of cell types we postulated that rhPDGF-BB might delay disc cell degeneration through inhibition of apoptosis. To address this hypothesis, we treated human IVD cells isolated from five independent patients with rhPDGF-BB in monolayer and 3D pellet cultures. The anti-apoptotic potential, cell proliferative capacity, morphology/pellet differentiation, and gene expression of PDGF-treated IVD cells were evaluated via flow cytometry/immunohistochemistry, MTT assays, histology, and quantitative RT-PCR, respectively. We found that rhPDGF-BB treatment significantly inhibited cell apoptosis, increased cell proliferation and matrix production, and maintained mRNA expression of critical extracellular matrix genes. This study suggests two possible mechanisms for the anti-degenerative effects of rhPDGF-BB on human IVD cells. First, PDGF treatment strongly inhibited IVD cell apoptosis in 3D cultures. Second, rhPDGF-BB acts as an anabolic agent, promoting maintenance of IVD cell phenotype in 3D culture, based on the molecular and protein expression analysis. We speculate that rhPDGF-BB may be used as a biologic treatment to target early degenerative IVD disease in the future., (© 2014 Orthopaedic Research Society. Published by Wiley Periodicals, Inc.)

Study Design: Preclinical animal study.Objective: Determine the in vivo effects of platelet-derived growth factor BB (PDGF-BB) delivered in a thiol-modified hyaluronic acid (TMHA) hydrogel on intervertebral disk (IVD) degeneration.Summary Of Background Data: IVD degeneration is a worldwide health concern and remains without an effective treatment. Several in vitro studies have demonstrated the potential of PDGF-BB, a primary component of platelet-rich plasma, as a therapy for IVD degeneration. Our hypotheses were that treatment of injured IVDs with PDGF would inhibit degeneration and that administration of PDGF in a TMHA hydrogel would improve its efficacy.Methods: IVD degeneration was induced using the rabbit annular puncture model. Four weeks after injury, IVDs were treated with either PDGF-BB or PDGF-BB delivered within a TMHA hydrogel. The efficacy of treatment was determined using x-ray, MRI, histology, and biomechanical testing.Results: At 4 weeks after treatment, cell apoptosis and deposition of matrix containing type III collagen a1 (Col3a1) was demonstrated in both the nucleus pulposus and annulus fibrosus, while this was inhibited by PDGF. At 8 weeks after treatment, disc area and MRI indices of injured IVDs treated with PDGF were significantly higher (P < 0.05) than those treated with the TMHA alone. Similarly, degenerative scores for saline- and TMHA-treated IVDs demonstrated significantly more degeneration (P < 0.05) than PDGF-treated IVDs at 8 weeks. Biomechanical assessments found fewer indicators of degeneration in PDGF-TMHA-treated IVDs at both 4 and 8 weeks post-treatment, compared to saline-, TMHA-, and PDGF-only-treated IVDs. Both PDGF- and PDGF-TMHA-treated IVDs also demonstrated a significant increase (P < 0.05) in compressive strength to failure, compared with controls at 8 weeks post-treatment.Conclusion: The results of this study suggest that PDGF-BB significantly decreases disc degeneration and when delivered in a TMHA gel scaffold, helps prevent both apoptosis and Col3 matrix production, while maintaining disc structure and biomechanical function.Level Of Evidence: NA. [ABSTRACT FROM AUTHOR]