title: Osteogenic protein 1 does not stimulate a regenerative effect in cultured human degenerated nucleus pulposus tissue.
abstract: Low back pain is a major cause of disability and is heavily associated with intervertebral disc degeneration. Osteogenic protein 1 (OP-1) is a growth factor that has shown potential to regenerate the intervertebral disc in human cells and animal models. However, high doses are required, presumably due to clearance from the tissue; controlled release may be a solution to this problem. In this study, we developed a preclinical, pathophysiological human tissue explant culture model of degenerated nucleus pulposus (NP). The NP explants were cultured for 28 days and injected with 100 µg OP-1 as a bolus, or with sustained-release biodegradable microspheres loaded with 16 or 1.6 µg OP-1. After culture, the tissue explants were analysed for biochemical content [water, sulphated glycosaminoglycans (GAGs), hydroxyproline and DNA], histology, cell viability and gene expression (disc matrix anabolic and catabolic markers). Untreated degenerated NP explants lost some of their GAG content when cultured for 4 weeks, but maintained other tissue constituents. Gene expression levels were close to native values. A bolus injection of OP-1 partially restored GAG content to the native level in half of the donors, while the sustained release of OP-1 did not affect the NP explants. No effect of treatment was observed on anabolic or catabolic gene expression at day 28. These results demonstrated that the regenerative potential of OP-1 is donor dependent, and only at very high doses. This questions the clinical use of OP-1 as a regenerative agent, as these high doses may increase the incidence of complications. Copyright © 2015 John Wiley & Sons, Ltd.
authors.affiliation: Orthopaedic Biomechanics, Department of Biomedical Engineering, Eindhoven University of Technology, The Netherlands.
authors.forename: Bart G M
authors.initials: BGM
authors.lastname: van Dijk
authors.affiliation: Orthopaedic Biomechanics, Department of Biomedical Engineering, Eindhoven University of Technology, The Netherlands.|Laboratoire de Bioingénierie et Biomécanique Ostéo-articulaire, UMR CNRS 7052, Université Denis-Diderot, Faculté de Médecine Lariboisière-Saint-Louis, Paris, France.
authors.forename: Esther
authors.initials: E
authors.lastname: Potier
authors.affiliation: DSM Ahead B.V., Geleen, The Netherlands.
authors.forename: Maarten
authors.initials: M
authors.lastname: van Dijk
authors.affiliation: Department of Orthopaedics, University Medical Centre Utrecht, The Netherlands.
authors.forename: Laura B
authors.initials: LB
authors.lastname: Creemers
authors.affiliation: Orthopaedic Biomechanics, Department of Biomedical Engineering, Eindhoven University of Technology, The Netherlands.|Department of Orthopaedics, University Medical Centre Utrecht, The Netherlands.
authors.forename: Keita
authors.initials: K
authors.lastname: Ito
mesh_terms: D055419:Bone Morphogenetic Protein 7 / Q000737:chemistry / Q000494:pharmacology; D004337:Drug Carriers / Q000737:chemistry / Q000494:pharmacology; D006801:Humans; D055959:Intervertebral Disc Degeneration / Q000188:drug therapy / Q000378:metabolism* / Q000473:pathology; D008863:Microspheres; D009924:Organ Culture Techniques; D012038:Regeneration
chemical_list: C525819:BMP7 protein, human; D055419:Bone Morphogenetic Protein 7; D004337:Drug Carriers
keywords: explant culture; growth factor therapy; intervertebral disc degeneration; nucleus pulposus; osteogenic protein 1; regenerative medicine