MSC as Veto Cells II

Baltimore, MD -

It is known that mesenchymal stem cells have veto-like properties. Essentially the veto cell inactivates, either through killing or induction of anergy, a cell that reacts against it. Theoretically, if the mesenchymal stem cells have veto-like properties, then this veto activity should be recognized in vivo by induction of immunological hyporesponsiveness to the administered cells.

In a recent study (Beggs et al. Immunologic consequences of multiple, high-dose administration of allogeneic mesenchymal stem cells to baboons. Cell Transplant. 2006;15(8-9):711-21) scientists at Osiris Therapeutics have administered high doses of purified mesenchymal stem cells (5 × 10(6) cells per kg) to baboons in absence of immune suppression to assess whether the veto activity can suppress T cell responsiveness against cells of the same origin as the infused mesenchymal stem cells. Additionally, the investigators assessed wither stem cells persisted in the allogeneic host in absence of immune suppression.

The investigators found that donor-specific inhibition of mixed lymphocyte reaction occured in the majority of baboons treated with mesenchymal stem cells. Additionally, the T cell response to conconavalin A was not inhibited. 50% of the treated animals still had mesenchymal cells when examined at 4 weeks after transplantation.

This study is an important step in the demonstration that antigen-specific immune modualtion can be induced through the veto activities of mesenchymal stem cells. Similar attempts to induce veto activity through manipulation of donor specific cells have occurred by Dr. Weiping Min's group who genetically engineered donor-dendritic cells with FasL in order to induce donor specific tolerance and increase allograft survival. The advantage of using donor specific mesenchymal cells is that these cells theoretically mediate their veto effects not just through the induction of responder cell apoptosis, but also through the generation of tolerance promoting T regulatory cells.