New Cell-Based Therapy Paradigm: Induction of Bone Marrow-Derived Multipotent Mesenchymal Stromal Cells into Pro-Inflammatory MSC1 and Anti-inflammatory MSC2 Phenotypes.

Cell-based therapies (CBTs) are quickly taking hold as a revolutionary new approach to treat many human diseases. Among the cells used in these treatments, multipotent mesenchymal stromal cells, also often and imprecisely termed mesenchymal stem cells (MSC), are widely used because they are considered clinically safe, unique in their immune-modulating capabilities, easily obtained from adult tissues, and quickly expanded as well as stored. However, despite these established advantages, there are limiting factors to employing MSCs in these therapeutic strategies. Foremost is the lack of a general consensus on a definition of these cells, marring efforts to prepare homogeneous lots and more importantly complicating their in vitro and in vivo investigation. Furthermore, although one of the most profound clinical effects of MSC intravenous administration is the modulation of host immune responses, no adequate ex vivo assays exist to consistently predict the therapeutic effect of each MSC lot in the treated patient. Until these issues are addressed, this very promising and safe new therapeutic approach cannot be used to its full advantage. However, these confounding issues do present exciting opportunities. The first is an opportunity to discover unknown aspects of host immune responses because the unique effect driven by MSC infusion on a patient's immunity has not yet been identified. In addition, there is an opportunity to develop methods, tests, and tools to better define MSCs and MSC-based therapy and provide consistency in preparation and effect. To this end, my laboratory recently developed a new approach to induce uniform pro-inflammatory MSC1 and anti-inflammatory MSC2 phenotypes from bone marrow-derived MSC preparations. I anticipate that MSC1 and MSC2 provide convenient tools with which to address some of these limitations and will help advance safe and effective CBTs for human disease.