Enucleated human mesenchymal stromal cells for the homing and the delivery of therapeutic cargos in vivo

The targeted delivery of therapeutics to diseased tissue enhances their efficacy and decreases their side effects. Here, we report enucleated mesenchymal stromal cells (MSC) as vehicles for the targeted delivery of therapeutic compounds. The cell nuclei are removed by density gradient centrifugation following the genetic integration of disease-targeting proteins that can be directed to improve the tissue-specific homing properties of the cells. Enucleated MSCs do not proliferate or permanently engraft in the host, yet retain organelles for energy and protein production, undergo integrin-regulated adhesion to inflamed endothelial cells, and actively home to chemokine gradients released by diseased tissues. In preclinical mouse models of acute inflammation and of pancreatitis, the systemic administration of enucleated MSCs, expressing two chemokine receptors and an adhesion molecule, improved the delivery of the cytokine interleukin-10 to target tissue, attenuating inflammation and ameliorating pancreatitis, compared to control exosomes and non-engineered MSCs. Enucleated MSCs are therapeutic delivery vehicles that bridge the functional properties of cells with the cargo-loading characteristics of extracellular vesicles and could be applied to treat a wide range of diseases.