The effect of Insulin Like Growth Factor I on matrix synthesis in engineered human tendon tissue

Abstract

Growth factors are essential during tissue formation and maintenance. In tendon tissue, insulin like growth factor I (IGF‐I) plays a key role in cell response to mechanical loading by increasing the production of extracellular matrix proteins. However, its role in formation and regeneration of human tendon is unknown. We hypothesized that IGF‐I improves neoformation of human tendon and particularly collagen synthesis. To study this, we engineered tendon‐like tissue from adult human tendon cells and exposed the tissue to medium with or without IGF‐I, respectively, supplemented with either 0.5% or 10% fetal bovine serum (FBS). The cells increased collagen type I, scleraxis and tenomodulin gene expression, and the total collagen protein content rose with supplementation of IGF‐I (p<.05). This increase can be partially explained by a higher collagen fibril diameter in the presence of IGF‐I (p<.05). It is intriguing that 10% FBS had an inhibitory effect on tendon matrix formation compared to 0.5% FBS and suggests that serum proteins inhibit matrix synthesis. These results demonstrate that IGF‐I enhances collagen production in human tendon‐like tissue and implicates potential treatment options following tendon injuries. The suppressive effect of highly concentrated FBS illustrates the challenge in subjecting cells to high dosages of various growth factors.(Financial Support: Nordea Fondation, Danish Medical Research Council)