A strategy to improve current MSC-based therapies (TECH1P.833)

Abstract

Abstract Mesenchymal stem cell (MSC) hold promise in the therapy of many inflammatory and degenerative disease. However, result from recent clinical trials using these cells are disappointing, suggesting that current MSC-based therapies need to be improved. We previously demonstrated that, immediately after their contact with serum following infusion, MSCs active complement of the innate immunity and are injured by the activated complement despite the presence of native cell surface complement regulators. In this work, we found that systemic administration of heparin, a widely used drug which is also a potent complement inhibitor, protects MSCs from serum-mediated damage after i.v. infusion. To minimize the side effects of systemic heparin administration, we also developed a method to paint heparin onto the surface of MSCs, We found that chemically modified heparin can be painted onto MSCs, and that these heparin-painted MSCs are better protected from serum (complement)-medicated attack and retain better immunosuppressive activity than regular MSCs. These data suggest that the cell surface engineering of MSC with heparin would be a simple and effective approach to improve the outcomes of current MSC-based clinical trials.