A Biophysically Defined Msc Subpopulation For Enhanced Homing And Immunosuppression

Aims:Systemically administered bone marrow (BM) mesenchymal stromal cells (MSCs) are potentially efficacious cell-therapies for the treatment of graft-vs-host disease (GVHD) or auto-immune complications. For infused MSCs to successfully resolve immune reactions, effective homing and biodistribution to target tissues are important pre-requisites and the delivered MSCs should also be biologically primed. However, retrospective studies have now demonstrated that MSCs, when ex vivoexpanded to reach numbers relevant for human use, are a heterogeneous cell population consisting of subpopulations with different functionalities. The overall non-uniform cellular properties result in unreliable biodistribution and immunosuppressive functions. A systematic study of expanded MSCs to discern useful subpopulations is hindered by the lack of unique surface markers. In lieu of immunophenotype, we hypothesized and verified that biophysical properties of MSCs can be a useful strategy for isolating unique subpopulations. Here, we will describe a clinically relevant biophysical strategy for deriving a primed MSC subpopulation that is equipped with the necessary properties for homing and immune suppression.