Knockdown of MicroRNA Let-7a Improves the Functionality of Bone Marrow-Derived Mesenchymal Stem Cells in Immunotherapy.

ABSTRACT: Bone marrow-derived mesenchymal stem cells (MSCs) have been recently used in clinical treatment of inflammatory diseases. Practical strategies improving the immunosuppressive property of MSCs are urgently needed for MSC immunotherapy. In this study, we aimed to develop a microRNA-based strategy to improve MSC immunotherapy. Bioinformatic analysis revealed that let-7a targeted the 3' UTR of mRNA of Fas and FasL, both of which are essential for MSCs to induce T cell apoptosis. Knockdown of let-7a by specific inhibitor doubled Fas and Fas ligand (FasL) protein levels in MSCs. Because Fas attracts T cell migration and FasL induces T cell apoptosis, knockdown of let-7a significantly promoted MSC-induced T cell migration and apoptosis in vitro and in vivo. Importantly, MSCs knocked down of let-7

SUBMITTER: Yu Y 

PROVIDER: S-EPMC5368594 | biostudies-literature | 2017 Feb

REPOSITORIES: biostudies-literature