Vascularised bone marrow tolerance induction attempt in transplanted limbs

An example of our current research at Microsearch involves the simultaneous transplantation of a donor limb and vascularised bone marrow (VBM) in a rat model.

Anastomosis of the femoral artery

Vascularised bone marrow is a composite tissue transplant, as it involves the introduction of a length of donor femur (bone from the upper hind limb) and localised blood vessels. These blood vessels are ducted off existing blood vessels in the recipient’s hind limb, to provide a fresh blood supply to the donor bone. This enables the bone implant to continue to manufacture bone marrow. As bone marrow is a source of important immune cells, its production changes the mechanisms involved in an immune response to donor tissue. The belief is that VBM will delay or reduce the rejection response to a donor limb, enabling us to reduce the quantity and duration of immunosuppressive drug therapy.

It is well established that immunosuppressive therapy carries associated side effects that include increased risks of developing cancer and diabetes. These risks compromise the ethics involved in limb transplantation, as the procedure returns independence to the recipient but does not increase the length of their life. A procedure, such as tolerance induction that allows drug therapy to be withdrawn, would then be beneficial to transplant recipients and mitigate the longer term health risks involved.