Limb Transplantation is no longer a myth but a reality with about two dozen people around the world  having received hand transplants. But Thomas Tung, M D  aplastic  and reconstructive  surgeon  at Barnes – Jewish Hospital, does not want  to be hands on , on this surgery, not until he has some answers.  Tung feels that the health risks that immunosuppressive drugs pose, and they are an integral part of all transplants, do not warrant hand transplants.  Long term use of immunosuppressive drugs  raises the  risk of infection and cancer because  thye weakened immune system is unable to ward off these threats. Furthermore  immune supprsion  therapy eventually fails , and transplanted organs  undergo rejection an average of 10 years after surgery.

Tung is looking for a way to produce permanent tolerance without the need for  any immunosuppressive  medication. And to that end, Tung is researching a mouse model where he is transplanting hind limbs to mice from unrelated donors without giving the mice immunosuppressive medications. Instead he is using co stimulation-blocking therapy, which is designed to induce tolerance to tissues in the transplanted hind limb. But not to globally suppress the immune system.  In this therapy the mice received an antibody that blocked the action of certain molecules important for the immune system’s T cells to attack foreign tissue.

In addition to the co-stimulation blockade, mice received donor bone marrow, either as an infusion or simply as the marrow present in the bones of the donor hind limb. Earlier research suggested that the donor  bone marrow could help  induce  transplant tolerance , and Tung found that  the small amount of bone marrow within the hind limb was as effective  as a  large infusion of bone marrow cells given intravenously.

While the co stimulation blockade/bone marrow therapy did not result in permanent tolerance of the transplanted hind limb, it greatly extended the time before the mice rejected the new limb. In one set of experiments, mice not given a co- stimulation blockade rejected their new limbs after  about 10 days, whereas  the muscles and bone of the transplanted  limb in co-stimulation blockade treated mice survived an average of 222 days.

“Research into co- stimulation blockade is relatively new,” Tung says. “And just over the last few years, half dozen new co-stimulation pathways have been recognised. Researchers have found that when you combine  several  antibodies to block several pathways  at once, it may increase the effectiveness of the therapy. That’s a big step toward tolerance of transplanted tissue.”  The next stage of Tung’s research will focus on these new co-stimulation blockers. In addition, Tung will collaborate with other researchers to investigate regeneration of nerves in transplanted limbs to help recipients improve functionality.