Abstract
Top of pageAbstract INTRODUCTION IGF-I improves tendon healing in vitro.1 Exogenous IGF-I improves healing of tendinitis lesions.2 Autologous mesenchymal stem cells (MSCs) provide a pool of pluripotent cells to enhance tendinitis repair. This study combined these two modalities by examining the therapeutic use of MSCs overexpressing IGF-I ligand. METHODS An adenoviral vector containing IGF-I (AdIGF-I) was assessed in MSCs to determine the optimal dose. MSC monolayers were transduced with AdIGF-I: 100, 250, 500, 750, and 1000 MOI. Monolayers were harvested on day 6 for analysis of IGF-I, collagen type I, and 18s mRNA. Two optimal viral doses were then assessed over time. Monolayers were harvested 2, 4, 8, 14, 21 and 28 days following transduction to determine gene expression of IGF-I, collagen type I, and 18S mRNA. Medium samples were utilized to determine IGF-I ligand levels. RESULTS MSCs transduced with adenoviral IGF-I expressed ligand at all experimental viral doses (Fig. 1). The optimal viral dose for enhanced IGF-I ligand production and minimal cytotoxic effects was 750 to 1000 MOI (Table 1). From the initial experiment, these two doses were examined over time. MSC expression of IGF-I message and ligand was significantly elevated in both viral doses, and remained significantly elevated throughout the course of 28 days in culture (Fig. 2). Medium IGF-I analysis confirmed therapeutic ligand levels. Collagen type I message was significantly elevated in the MSC cultures with AdIGF-I 48 hours post transduction. DISCUSSION MSCs produced therapeutic levels of ligand for 14 days following transduction. IGF-I tissue levels lag for 2 weeks following tendinitis injury.3 Utilizing MSCs as a vehicle for gene transfer and lesion healing is a logical therapeutic option; autogenous cell populations reduce immunoreactivity and extend ligand production. Adenoviral gene therapy in vivo avoids exogenous re-supplementation with recombinant IGF-I. Additionally, AdIGF-I transduced MSCs released IGF-I for 2 weeks, correlating to the initial phases of tendon healing. This study indicates AdIGF-I transduced mesenchymal stem cells may improve tendon healing.
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