Scientists managed to trick the immune system of rats and successfully transplanted them limb from historiallisia donor, using the tactics of cancer cells. Tumors secrete CCL22 chemokine — this substance attracts regulatory T cells that block immune response. To simulate this mechanism, animals after transplantation implanted polymer microparticles, which are small doses allocated CCL22. In the end of the limb has taken root and functioned successfully for over 200 days. Article published in the journal Science Advances.
Vascularized composite allotransplantation is a relatively new kind of transplant organs, particularly of the limbs or face, from one person to another. The main problem of all types of transplants — the risk of rejection when the immune system of the recipient encounters with alien to her tissue donor. Therefore, people with transplants have a lifetime to take immunosuppressants, which have many serious side effects.
There is an alternative approach that allows to take the immunosuppressants: you can, for example, to use the mechanisms that the body uses to configure your immune system. A major role in the control of the immune response play a regulatory T-lymphocytes, or T-suppressors. Recruit T-cells can tumor to trick the immune system, which is able to destroy them. Tumor cells secrete chemokine CCL22, which connects with the CCR4 receptors of T-suppressor cells and inhibits the immune response.
In order to simulate the tumor cell and its strategy of attracting regulatory T lifotsitov, scientists have created a synthetic microparticle, which secretes CCL22 and supports its gradient in the tissues of the body. Particles that were implanted rats, really was attracted to T-suppressor and eliminated the inflammation in models of periodontitis and dry keratoconjunctivitis.
James Fisher (James Fisher) from the University of Pittsburgh and his colleagues used micro-particles, which secrete CCL22 to control the immune response of the rat on the allograft of the anterior limbs. Microparticles were made of a biocompatible and biodegradable polymer. Due to the porous structure, they isolated chemokine gradually (over 40 days) and small doses (in nanograms).
Microparticles were implanted subcutaneously in the transplanted limb immediately after surgery and again three weeks later. During the first three weeks after transplantation animals were also injected with immunosuppressants according to the standard Protocol to be sure that the transplant has successfully engrafted, then canceled them.
The condition of the graft was assessed visually for 200 days for histochemical studies of biopsied muscle and skin. Then the three animals transplanted three pieces of skin from different donors: immunocompetence, the same from whom the transplanted limb and the third are incompatible. No further treatment of these rats had received. So, researchers evaluated how the generated immunotolerance was specific to the donor.
Limb successfully engrafted in the animals, which were injected microparticles, and functioned for 200 days of observation. The body control animals rejected the graft within two to three weeks after discontinuation of immunosuppressants. A single administration CCL22 also didn’t help limbs to settle down.