Insulin-like growth factor-I enhances cell-based repair of articular cartilage

Abstract

Composites of chondrocytes and polymerised fibrin were supplemented with insulin-like growth factor-I (IGF-I) during the arthroscopic repair of full-thickness cartilage defects in a model of extensive loss of cartilage in horses. Repairs facilitated with IGF-I and chondrocyte-fibrin composites, or control defects treated with chondrocyte-fibrin composites alone, were compared before death by the clinical appearance and repeated analysis of synovial fluid, and at termination eight months after surgery by tissue morphology, collagen typing, and biochemical assays. The structure of cartilage was evaluated histologically by Toluidine Blue reaction and collagen type-I and type-II in situ hybridisation and immunohistochemistry. Repair tissue was biochemically evaluated by DNA assay, proteoglycan quantitation and characterisation, assessment of collagen by reverse-phase high-performance liquid chromatography, and collagen typing using cyanogen bromide digestion and peptide separation by polyacrylamide gel electrophoresis. The results at eight months showed that the addition of IGF-I to chondrocyte grafts enhanced chondrogenesis in cartilage defects, including incorporation into surrounding cartilage. Gross filling of defects was improved, and the tissue contained a higher proportion of cells producing type-II collagen. Measurements of collagen type II showed improved levels in IGF-I-treated defects, supporting in situ hybridisation and immunohistochemical assessments of the defects. IGF-I improves the repair capabilities of chondrocyte-fibrin grafts in large full-thickness repair models.

Adenoviral-mediated transfer of TGF-β1 but not IGF-1 induces chondrogenic differentiation of human mesenchymal stem cells in pellet cultures

“…Concentrations of IGF-1 as low as 50 ng/mL are sufficient to exert significant effects on the proliferative and metabolic functions of cultured chondrocytes [6,13,31,34,44]. IGF-1 may therefore be more effective on differentiated chondrocytes than inducing chondrogenic differentiation of MSCs.…”

“…Insulin-like growth factor-1 (IGF-1) has been extensively investigated for use in cartilage repair and regeneration [26][27][28][29][30][31][32][33]40]. Most studies on IGF-1 have focused on its effects on mature chondrocytes.…”

Gene delivery to cartilage defects using coagulated bone marrow aspirate

“…1 It might be possible to improve the effectiveness of this repair response through controlled administration of recombinant proteins known to promote chondrogenesis of mesenchymal progenitor cells or increased synthesis of cartilage matrix components by chondrocytes. Recombinant growth factors such as BMP-2, 12-15 IGF-1 15,16 and TGF-b [17][18][19][20] have shown promise in studies of cartilage repair and regeneration; 14,18,21 however, the full reparative potential of these and other proteins is compromised by delivery problems and rapid clearance from the joint. The use of gene therapy as a system to achieve sustained, localized protein delivery within an osteochondral lesion may overcome these limitations.…”

Dynamic matrix composition in engineered cartilage with stochastic supplementation of growth factors

“…It has been observed experimentally by several investigators that growth factors play an important role in matrix production and inhibition, but there is limited knowledge about the functional mechanisms associated with these effects. [16][17][18][19][20][21][22] This leads to the present objective which is to explore the influence of growth factors within engineered cartilage by modelling hypothetical characteristics of ECM synthesis.…”