Mesenchymal stem cells (MSCs) have been regarded as potential targeting vehicles and demonstrated to exert therapeutic benefits for brain diseases. Direct homing to diseased tissue is crucial for stem cell-based therapy. In this study, a peptide-based targeting approach was established to enhance cell homing to cerebral ischemic lesion. Palmitic acid-peptide painted onto the cell membrane was able to direct MSCs to ischemic tissues without any observed cell cytotoxicity and influence on differentiation, thus reducing accumulation of cells in peripheral organs and increasing engraftment of cells in the targeted tissues. With enhanced cell homing, MSCs were used to deliver miR-133b to increase the expression level of miR-133b in an ischemic lesion and further improve therapeutic effects. This study is the first to develop MSCs co-modified with targeting peptide and microRNAs as potential targeting therapeutic agents. This targeting delivery system is expected to be applicable to other cell types and other diseases aside from stroke
