Application of Tolerogenic Dendritic Cells for Hematopoietic Stem Cell Transplantation

The immune system protects us from invading pathogens, but has to be kept in check to prevent harmful responses to our own tissues. Unique immune “suppressor” cells have been recently characterized that prevent harmful responses to our own cells and proteins. We have recently identified unique populations of white blood cells, called dendritic cells that can induce the development of such “suppressor” cells. More importantly these immunosuppressive dendritic cells are unique in that they have special molecules on their cell surface that target them to tissues in the body where autoaggressive immune cells are either killed off or shut down during the development of the immune system.

We wish to (i) expand and isolate populations of dendritic cells based on their cell surface expression of these special trafficking molecules and then (ii) use them as facilitator cells in transplants of stem cells from a foreign donor. The idea behind our approach in stem cell transplantation therapy is that immunosuppressive dendritic cells from donor A will educate the immune system in recipient B to recognize cells and proteins from the donor as self and not to mount destructive rejection responses to stem cell grafts from the same donor (A).

Finally we wish to use a preservation protocol in formalin-based solvents to maintain the immunosuppressive attributes of these dendritic cells forever. That way they can be safely administered to patients that receive mismatched stem cell grafts without ever worrying that the function of these dendritic cells will change after injection into the patient. We will work to establish protocols for the use of immunosuppressive dendritic cells as facilitator cells for foreign stem cell grafts in the clinic.