The diverse immunomodulatory properties of mesenchymal stem/stromal cells (MSCs) could be

The diverse immunomodulatory properties of mesenchymal stem/stromal cells (MSCs) could be exploited for treatment of a multitude of inflammatory conditions. Nevertheless whether rejection of donor MSCs influences the efficacy of allogeneic MSC therapies is not known and no definitive clinical advantage of autologous MSCs over allogeneic MSCs has been demonstrated to date. Although MSCs may exert therapeutic function through a brief ‘hit and run’ mechanism protecting MSCs from immune detection and prolonging their persistence may improve clinical outcomes and prevent patient sensitization toward donor antigens. MSCs were Metoprolol tartrate originally identified by Friedenstein in mouse bone marrow and were characterized according to their multilineage potential1-3. Caplan later referred to these cells as mesenchymal stem cells4 yet to date rigorous demonstration of their stem cell properties has not been established. As a result of their original identification in the bone marrow many referred to them as “bone marrow stromal cells.” However MSCs have since been shown to be derived from both pericytes and adventitial progenitor cells from nearly all tissues5 6 Thus it may be appropriate to refer to MSCs as “multipotent perivascular-derived cells.” Regardless the issue of MSC nomenclature remains contentious. As of December 17 2013 there were 18 284 references in PubMed to “mesenchymal stem cell” or “mesenchymal stem cells ” 14 586 to “mesenchymal stromal cell” or “mesenchymal stromal cells ” 4 254 to “bone marrow stromal cell” or “bone marrow stromal cells ” and 183 to “multipotent stromal cell” or “multipotent stromal cells.” Irrespective of the nomenclature it is still unclear if the MSC phenotype exists work. Although pericytes and MSCs share properties and it is possible that when pericytes become activated and leave vessels they differentiate into MSCs this has not been conclusively demonstrated. In 2006 the International Society for Cellular Therapy established minimal criteria for designating a cell an MSC9; these include tri-lineage differentiation potential (osteogenic adipogenic and chondrogenic) cell-surface expression of CD90 CD105 and CD73 and lack of cell surface CD45 CD34 CD14 CD79 and HLA-DR. However culture-expanded MSCs consist of a heterogeneous population of cells exhibiting a spectrum of phenotypes and functional properties and the extent of these properties is dependent on the tissue donor and species of origin isolation technique culturing protocols and media used and passage number. That said heterogeneity is not Mouse monoclonal to ERBB3 unique to MSCs as clones of hematopoietic stem cells for example can exhibit considerable functional heterogeneity after transplantation10 11 In addition the clinical value of MSCs thus far seems primarily derived from their non-stem/progenitor cell properties. Namely MSCs produce extracellular vesicles including exosomes and a multitude of cytokines and growth factors that suppress immune responses by inhibiting B- and T-cell proliferation and monocyte maturation and by promoting Metoprolol tartrate generation of regulatory T cells and M2 macrophages12-15. Therefore although some argue that MSCs should be defined based on differentiation potential or ability to support hematopoiesis16 17 others advocate for a broader definition that places less emphasis on the ‘stem’ properties of the cell and more on the trophic and immunomodulatory properties that render them potentially useful in treating numerous diseases18-22. As the trophic Metoprolol tartrate and immunomodulatory properties of MSCs are largely responsible for the rapid rise in the therapeutic exploration of major histocompatibility (MHC)-unmatched allogeneic MSCs a broader definition of MSCs that includes these properties is more applicable to this Perspective. Metoprolol tartrate It is also important to consider that MSCs can easily be manipulated in culture to obtain phenotypes that more effectively treat one disease over another; these modified cells may still be considered MSCs in the broad sense without necessarily meeting all of the minimal criteria defined by the 2006 definition. Given the general lack of rigorous MSC phenotype assessment in the published literature adopting a narrower definition of MSCs would preclude us from writing this Perspective. Therefore here we consider MSC to be cells that are generally defined by the 2006 minimal criteria. Positive data from preclinical models and elucidation of the immunomodulatory properties of.