MSC = Veto cells

Duarte, CA -

It is known that mesenchymal stem cells are potent immune modulators. The methods by which they inhibit various inflammatory reactions include production of immune suppressive cytokines such as IL-10, induction of tryptophan depletion using the enzyme IDO, and providing signal 1 in absense of costimulation.

The immune suppressive properties of mesenchymal stem cells make them an interesting population for use as "veto cells". Essentially a veto cell is a cell that is recognized by an immune response, but then goes and specifically silences the immune response directed against it.

In the current paper (Itakura et al.Mesenchymal stem cells facilitate the induction of mixed hematopoietic chimerism and islet allograft tolerance without GVHD in the rat. Am J Transplant. 2007 Feb;7(2):336-46)allogeneic mesenchymal stem cells were utilized in order to induce donor-specific tolerance through stimulating chimerism. Recipient rats had their islets ablated by the antibiotic streptozoicin. Subsequently they were transplanted with islets from genetically incompatible rats. The islets were rejected initially, however tolerance was induced when donor specific mesenchymal cells were added along with the islets.

Tolerance was noted in that not only islets were accepted but also donor-specific but not third party skin grafts were accepted.

Tolerance was also promoted by administration of the immune suppressive drug DSG.

This paper supports the continued investigation of mesenchymal stem cells as "veto cells"