Effects of Insulin-Like Growth Factor I on Transforming Growth Factor β1 Induced Chondrogenesis of Synovium-Derived Mesenchymal Stem Cells Cultured in a Polyglycolic Acid Scaffold

Abstract

The aim of this study was to demonstrate the induction of chondrogenesis by transforming growth factor (TGF)-β₁ from synovium-derived mesenchymal stem cells in a three-dimensional polyglycolic acid (PGA) scaffold, and to evaluate the effects of insulin-like growth factor (IGF)-I on TGF-β₁-induced chondrogenesis. Adult human synovial membranes were obtained from the knees of patients with osteoarthritis or rheumatoid arthritis. Cells were expanded in monolayers, seeded onto a PGA scaffold, and cultured for 4 or 8 weeks in chondrogenic medium containing TGF-β₁ with or without IGF-I. As a control, the cells were cultured in chondrogenic medium without TGF-β₁. The glycosaminoglycan content was quantified using dimethylmethylene blue dye-binding assay, and the DNA content was measured fluorometrically. Histological examination was also performed using safranin-O staining. The expression of mRNA for aggrecan and collagen type II was confirmed by RT-PCR. After 4 weeks of cultivation with TGF-β₁, the cells differentiated to a chondrocytic phenotype, and these chondrogeneses were more potent when cultured for 8 weeks. The combination of IGF-I and TGF-β₁ produced higher amounts of glycosaminoglycan than TGF-β₁ alone at 8 weeks. In conclusions, chondrogenesis from human synovium-derived mesenchymal cells was identified, and IGF-I plays a role in maintaining the extracellular matrix in combination with TGF-β₁.