Enhanced Homing of CXCR-4 Modified Bone Marrow-Derived Mesenchymal Stem Cells to Acute Kidney Injury Tissues by Micro-Bubble-Mediated Ultrasound Exposure

Although the curative effects of bone marrow stromal cells (BMSCs) for acute kidney injury (AKI) have been recognized, their in vivo reparative capability is limited by the low levels of targeted homing and retention of intravenous injected cells. Stromal cell-derived factor-1 (SDF-1) plays an important role in stem cell homing and retention through interaction with its specific functional receptor, CXCR4, which is presumably related to the poor homing in AKI therapy. However, most of the functional CXCR4 chemokine receptors are lost upon in vitro culturing. Ultrasound-targeted micro-bubble destruction (UTMD) has become one of the most promising strategies for the targeted delivery of drugs and genes. To improve BMSC homing to AKI kidneys, we isolated and cultured rat BMSCs to third passage and enhanced CXCR-4 transfection efficiency in vitro by applying UTMD and polyethylenimine. Transwell migration assay showed that the migration ability of CXCR4-modified BMSCs was nine-fold higher than controls. Then, mercuric chloride-induced AKI rats were injected with transfected BMSCs through their tail veins. We showed that enhanced homing and retention of BMSCs were observed in the CXCR-4 modified group compared with other groups at 1, 2 and 3 d post-treatment. Collectively, our data indicated that UTMD was an effective method to increase BMSCs' engraftment to AKI kidney tissues by increasing CXCR-4 expression.