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Osteogenic protein 1 does not stimulate a regenerative effect in cultured human degenerated nucleus pulposus tissue
Author(s) -
Dijk Bart G. M.,
Potier Esther,
Dijk Maarten,
Creemers Laura B.,
Ito Keita
Publication year - 2017
Publication title -
journal of tissue engineering and regenerative medicine
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.835
H-Index - 72
eISSN - 1932-7005
pISSN - 1932-6254
DOI - 10.1002/term.2111
Subject(s) - anabolism , explant culture , glycosaminoglycan , intervertebral disc , hydroxyproline , extracellular matrix , catabolism , chemistry , tissue culture , decellularization , microbiology and biotechnology , intervertebral disk , proteoglycan , histology , matrix (chemical analysis) , tissue engineering , andrology , pathology , anatomy , biology , in vitro , medicine , biochemistry , biomedical engineering , metabolism , chromatography , lumbar
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.