Small intestinal submucosa as a potential bioscaffold for intervertebral disc regeneration.

STUDY DESIGN: To evaluate the capacity of porcine small intestine submucosa to support the in vitro proliferation of human disc cells and the synthesis of extracellular matrix that could restore the biochemical properties of the disc. OBJECTIVE: To evaluate if porcine small intestine submucosa is a potential bioactive scaffold for rescuing degenerative disc cells. SUMMARY OF BACKGROUND DATA: Discogenic back pain is associated with alterations of the disc and abnormal turnover of the disc extracellular matrix. We hypothesize that a biodegradable and biocompatible acellular scaffold such as small intestine submucosa, which contains entrapped growth factors, may stimulate disc cells to synthesize extracellular matrix, thereby arresting the degeneration, or even promoting the regeneration, of the disc. METHODS: Human degenerative anulus and nucleus cells were seeded onto small intestine submucosa scaffolds, and evaluated over a 3-month period for cell growth (proliferation assay, deoxyribonucleic acid content) and matrix composition (glycosaminoglycan and collagen contents). RESULTS: As hematoxylin and eosin staining revealed, more than 70% of seeded cells attached to the small intestine submucosa surface and invaded throughout the scaffold. The macroscopic appearance of cell-seeded scaffolds was dramatically modified over time. Cell metabolic activity was confirmed for up to 3 months. Seeded scaffolds showed a higher glycosaminoglycan content as compared to control scaffolds. Toluidine blue staining detected large areas of proteoglycans. Positive gene expression for collagens I, II, and X, aggrecan, and Sox-9 confirmed deposition of new extracellular matrix components. CONCLUSIONS: This pilot study shows that small intestine submucosa is a promising bioactive material that could potentially serve as a temporary scaffold for intervertebral disc regeneration.

Lipoxygenase and prostaglandin G/H synthase cascades in cardiovascular disease.

The 12/15-lipoxygenase (LO) cascade governs the generation of 12-hydroperoxy-eicosatetraenoic acid (HPETE) and 15-HPETE from arachidonic acid. The 5-LO pathway plays a fundamental role in the biosynthesis of leukotrienes, essential inflammatory lipid mediators. Cyclooxygenase (COX)-1 and -2 biosynthetic pathways are responsible for prostaglandin and thromboxane formation. Experimental investigations in animal models using 12/15-LO deficient mice, 12/15-LO or 15-LO transgenic mice, or pharmacological 15-LO inhibition have all demonstrated the essential role of 12/15-LO in atherogenesis. The underlying mechanisms are linked to low-density lipoprotein oxidation, pro-inflammatory Th1 cytokine production and enhanced monocyte-endothelial cell interaction. Human genetic studies as well as disruption of the 5-LO gene in mouse models of hyperlipidemia revealed that 5-LO and 5-LO-activating protein are associated with risks of human cardiovascular disease, and that this cascade plays an important role in aortic aneurysm pathogenesis through leukotriene-mediated inflammatory chemokine production. COX-1 plays an active role in atherogenesis via thromboxane A(2), while COX-2-derived prostaglandin (PGI(2)) protects against atherosclerosis in murine models. Recent data demonstrated that selective inhibition of COX-2 augments the risk of cardiovascular events in patients. Selective inhibition or blockade of selective components in these two enzymatic pathways through systemic drug delivery or medical device approaches (e.g., drug-eluting stents) may have therapeutic benefit against certain cardiovascular diseases.