Nongenetic surface engineering of mesenchymal stromal cells with polyvalent antibodies to enhance targeting efficiency.

Systemic infusion is a prevalent administration method for mesenchymal stromal cells (MSCs) in clinical trials. However, the inability to deliver a large number of therapeutic cells to diseased tissue is a substantial barrier. Here, we demonstrate that surface engineering of MSCs with polyvalent antibodies can effectively improve the targeting efficiency of MSCs to diseased tissue. The polyvalent antibody is directly synthesized on the cell surface via DNA template-directed biomolecule assembly. The data show that engineered MSCs exhibit superior adhesion to inflamed endothelium in vitro and in vivo. In female mouse models of acute inflammation and inflammatory bowel disease, engineered MSCs show enhanced targeting efficiency and therapeutic efficacy in damaged tissues. Notably, the entire procedure for polyvalent functionalization only requires the simple mixing of cells and solutions under physiological conditions within a few hours, which significantly reduces preparation processes and manufacturing costs and minimizes the impact on the cells. Thus, our study provides a strategy for improved MSC-based regenerative medicine.