Effect of Modulating Oxidative Stress in Transplanted Mesenchymal Stem Cells during Ligament Healing

The increased clinical knee ligament injuries have necessitated the demands for an increased understanding of the healing process and methods to enhance it. We have previously demonstrated the cellular senescence occurring in rabbit ligaments during healing. Such stress induced senescence resulted in a senescence associated secretory phenotype(SASP). Physiology of SASP is not yet completely understood in ligament healing. Recently, micro RNA crosstalk with p53 is suggested playing a pivotal role in TGF-β signaling. In addition CD44-Epidermal Growth factor signaling pathway impairment also is a mechanism in delayed wound closure. Despite our preliminary study and literature has shown upregulation of CD44 in the senescent fibroblast, it is not clear whether the how micro RNA regulate the CD44 expression and its interaction with EGF downstream effectors. Moreover, reactive oxygen species (ROS) and mechanistic target of rapamycin (mTOR) is associated with senescence and their effect on hyaluronate-CD44 interaction and EGF downstream effectors is also unclear. Third, vascular endothelial growth factor(VEGF) increase in senescent cells and has been shown a chemotactic attraction to mesenchymal stem cells which lead to the hypothesis that it affect the CD44 expression. The purpose of this study is (1) to investigate the miRNA on the functions of CD44 in senescent fibroblast during ligament healing.(2) to investigate the effect of ROS as well as mTOR on CD 44 in senescent fibroblast during ligament healing. (3) to investigate the interaction between ROS as well as mTOR and CD 44 and its involvement in cellular migration (4) to investigate the effect of vascular endothelial growth factor (VEGF) on CD44 in senescent fibroblast during ligament healing.(5) to investigate effect of ROS/mTOR on the interaction of VEGF and CD44 in senescent fibroblast.(6) to investigate the functions of CD44 on transplanted mesenchymal stem cells during ligament healing.(7) to investigate the functions of CD44 on mesenchymal stem cell by modulating reactive oxygen species.(8) to investigate the survival of those pretreated cells in healing ligaments and functions of the transplanted ligament. Through this study, we can establish a HA-CD44 centered model for designing intervention strategy.

Project ID:PC10401-0588
External Project ID:MOST103-2314-B182-065-MY3