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Enhancing Efficacy of Bone Marrow Transplant

Huang et al. Blood. [Epub ahead of print]

Bone marrow transplantation has cured many patients of hematological diseases such as leukemias and lymphomas. Additionally, bone marrow transplantation is becoming used more and more in treatment of autoimmune diseases such as type 1 diabetes and multiple sclerosis. Unfortunately, there are still numerous limitations to this procedure. One of the biggest ones is that occurrence of graft versus host disease, in which the transplanted stem cells produce immune cells that attack the recipient. The other major problem is graft failure, in which the transplanted stem cells do not “take”.

The group of Dr. Ildstad from the University of Louisville has been working on enhancing bone marrow transplantation by co-administration of other cells called “facilitator cells.” In a recent publication (Huang et al. CD8{alpha}+ plasmacytoid precursor DC induce antigen-specific regulatory T cells that enhance HSC engraftment in vivo. Blood. 2010 Dec 29) it was shown that a type of dendritic cell, called the plasmacytoid dendritic cell, is capable of promoting bone marrow transplant efficacy through stimulation of T regulatory cells.

The scientists demonstrated that after bone marrow transplant from mismatched donors, there are immune suppressive cells, called T regulatory cells, that develop under specific conditions that stop the new (donor derived) immune system cells from attacking the recipient. When a mismatched bone marrow transplant is performed together with plasmacytoid dendritic cells, these cells “instruct” the donor immune system to generate T regulatory cells, which prevent graft versus host disease.

Implications of this research may be profound in areas outside of bone marrow transplantation for leukemias. In solid organ transplants, patients are required to take life-long immune suppressants to prevent the transplanted organ from being rejected. If donor bone marrow transplantation is performed with the donor organ, then the body does not reject the organ. Unfortunately this is not possible because bone marrow transplantation has a high risk of graft versus host disease. If the discovery of Dr. Ilstad’s group can be translated to humans, it may be possible to induce “immunological tolerance”, which is a state of immune un-responsiveness to the transplanted organ, while maintaining a functioning immune system towards pathogens and bacteria.

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