Mesenchymal Stromal Cell‐Mediated Treatment of Local and Systemic Inflammation through the Triggering of an Anti‐Inflammatory Response
Jonathan O. Martinez, Michael Evangelopoulos, Ava Brozovich, Guillermo Bauza, Roberto Molinaro, Claudia Corbo, Xuewu Liu, Francesca Taraballi, Ennio Tasciotti
Abstract
Abstract The emergence of cell‐based therapeutics, specifically the use of mesenchymal stromal/stem cells (MSCs), stands to significantly affect the future of targeted drug delivery technologies. MSCs represent a unique cell type, offering more than only regenerative potential but also site‐specific inflammatory targeting and tissue infiltration. In this study, a versatile multicomponent delivery platform, combining MSC tropism with multistage nanovector (MSV)‐mediated payload delivery, is debuted. It is demonstrated that the incorporation of drug‐loaded MSVs bestows MSCs with the ability to transport anti‐inflammatory payloads, achieving a fivefold increase in payload release without negatively impacting cellular functions, viability, extravasation, and inflammatory homing. When incorporated within MSCs, MSVs avoid rapid sequestration by filtering organs and conserve a 15‐fold increase in local inflammatory targeting compared to healthy ears. Furthermore, this MSC‐mediated MSV platform (M&Ms) rapidly triggers a 4.5‐fold reduction of local inflammation compared to free drug and extends survival to 100% of treated mice in a lethal model of systemic inflammation.