Therapeutic Effect of Pioglitazone-Pretreated Human Wharton’s Jelly-Derived Mesenchymal Stem Cells in a Rat Tendon Injury Model

The clinical application of mesenchymal stem cells (MSCs) has several limitations owing to their less therapeutic efficacy.Effect enhancement and MSCs from new sources might help in overcoming these limitations.The aim of the present study was to investigate the therapeutic effects of human Wharton's jelly-derived MSCs (hWJMSCs) and pioglitazone-pretreated MSCs (Pio-MSCs) in a rat tendon injury model.Fifty-four Sprague Dawley rats were randomly assigned to three groups: phosphate-buffered saline (PBS) group, implanted with PBS; MSC group, implanted with MSCs; and Pio-MSC group, implanted with Pio-MSCs.The cell or PBS with fibrin glue mixture was implanted around bilateral window defect in the Achilles tendons of the rats.The cross-sectional area measurement, histological analysis, gene expression, protein expression, and biomechanical analysis were performed at 2 and 4 weeks after modeling.Pio-MSC group revealed a significantly higher gene expression level of Col3 than PBS group at 2 weeks and that of TnC at 2 and 4 weeks.Moreover, MSC group revealed significantly higher gene expression level of Col1 than PBS group at 2 weeks.In general, the expression levels of Col1, Col3, Scx, and TnC were the highest in Pio-MSC group, followed by MSC and PBS groups.Furthermore, Pio-MSC group revealed significantly higher tenascin C-stained fraction than PBS group at 4 weeks.These findings suggest a potential role of hWJMSCs in tendon regeneration; however, the in vivo enhancement effect of pioglitazone pretreatment over MSC alone was not confirmed, and no differences were observed in histological or biomechanical outcomes among the groups.