Mesenchymal Stem Cells and IDO

Verona, Italy -

Mesenchymal stem cells are currently in Phase III of clinical trials in the US and are available as a fee for service in places such as Cellmedicine for the treatment of autoimmune/inflammatory conditions.

A fundamental question, however, is what are the mechanisms by which mesenchymal stem cells inhibit pathological inflammation?

This question seems to have been answered, at least in part, by a recent paper (Krampera et al. Role for interferon-gamma in the immunomodulatory activity of human bone marrow mesenchymal stem cells. Stem Cells. 2006 Feb;24(2):386-98).

The authors made several important findings:

1. Mesenchymal stem cells inhibit proliferation of T cells and NK cells but not B cells.

2. Mesenchymal stem cells do not cause upregulation of T regulatory cells. This point is in contradiction with other studies that have shown mesenchymal stem cells upregulate Treg activity.

3. T cell suppression by mesenchymal stem cells was contact independent BUT was dependent on production of IFN-gamma by T cells/NK cells.

4. The IFN-gamma acts to upregulate indoleamine 2,3-dioxygenase activity on mesenchymal cells.

5. The upregulation in IDO in turn depletes tryptophan, produces T cell apoptosis-inducing metabolites, and as a result inhibits T cell responses.