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Tooth Stem Cells Take a Bite Off T Cell Proliferation

Ding et al. Cells Tissues Organs., January 14, 2010

Mesenchymal stem cells are known classically to be capable of generating bone, fat, and cartilage tissues, and more recently have been demonstrated to have ability to become brain cells, liver cells, pancreas cells, and muscle cells.  The original studies on mesenchymal stem cells used bone marrow as the originating tissue, with subsequent studies having identified these cells in fat, muscle, and menstrual blood.  For a description of mesenchymal stem cells, please view this video http://www.youtube.com/watch?v=8WzalE5hLUs

Recently mesenchymal stem cells have been identified in deciduous (baby) teeth, as well as wisdom teeth.  Given the ease of tooth collection several companies have started banking tooth derived stem cells for future use, in a similar manner to which cord blood cells are banked.  Potential uses of mesenchymal stem cells include regeneration of injured tissue.  For example the company Osiris has recently released clinical trial data demonstrating that intravenous administration of bone marrow derived mesenchymal stem cells results in patient improvements after heart attacks.  Additionally, because these cells produce immune modulatory factors, mesenchymal stem cells have been used with success in treatment of autoimmune conditions in mice and man.

Unfortunately the major work on mesenchymal stem cells has focused on cells derived from the bone marrow, with some studies discussing cells from the cord blood.  Despite ease of tissue acquisition, relatively little is known about tooth derived mesenchymal stem cells.  A recent paper (Ding et al. Suppression of T Cell Proliferation by Root Apical Papilla Stem Cells in vitro.  Cells Tissues Organs. 2010 Jan 14) examined the immunological properties of these cells using an in vitro system.

The investigators grew mesenchymal stem cells from teeth of pigs in order to generate a source of cells that can be used for future in vivo experiments.  The cells had some characteristics of bone marrow derived mesenchymal stem cells in that they expressed low concentrations of the immune stimulatory molecule Swine Leukocyte Antigen (SLA) I, which is the porcine equivalent of HLA I, as well as absence of SLA II. 

Mixing of pig peripheral blood mononuclear cells with the compound phytohemagluttanin is known to result in stimulation of proliferation of the T cell component of the mononuclear cells.  When these stimulated T cells are placed in the presence of porcine mesenchymal stem cells, a dose dependent suppression of proliferation was observed.  This in vitro model of T cell activation was also confirmed in a scenario where T cells were purposely mis-matched antigenically with the mesenchymal stem cells and it was observed that the cells did not stimulate T cell proliferation.  Addition of mesenchymal stem cells to a mixed lymphocyte reaction in which T cells are activated in response to other T cells resulted in the inhibition of T cell proliferation. 

Mechanistically it was determined that inhibition of T cell proliferation was occurring through secretion of a soluble factor by the mesenchymal stem cells that does not induce killing of the activated T cells.  This poses the question if the mesenchymal stem cells were not just inhibiting proliferation but also activating T regulatory cells that are known to protect against pathological autoimmunity.  Previous studies have demonstrated that bone marrow mesenchymal stem cells generate T regulatory cells (Di Ianni et al. Mesenchymal cells recruit and regulate T regulatory cells. Exp Hematol. 2008 Mar;36(3):309-18).  In fact, generation of T regulatory cells has been described as one of the mechanisms in which stem cell therapy works against rheumatoid arthritis http://www.youtube.com/watch?v=NhNvy6YyLtc.

The ability to use stem cells to inhibit T cell responses has many therapeutic applications.  The current paper is one of the first to demonstrate that tooth derived mesenchymal stem cells, like their cousins from the fat and bone marrow, are capable of inhibiting immune responses that previously were pathological. 



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