For people dealing with the life-changing and often devastating aftermath of disfiguring injuries or the loss of limbs, minimal reconstruction using the patients’ own tissues may not be a sufficient remedy for some patients. Face and limb transplantation, known as Vascularized Composite Allotransplantation (VCA), requires multiple types of tissue to successfully function, these may include skin, muscle, nerves, and blood vessels. As with organ transplantation, VCA also necessitates the use of drugs, known as immunosuppressants, to stop the host immune system rejecting the foreign transplant tissue, a regimen that lasts for life. However, immunosuppressive drugs cause a host of adverse events. Now, a study from researchers at the University of Pittsburgh engineers artificial microparticles that trick the recipient’s immune system into accepting donor transplanted tissue as its own. The team states their synthetic particle biomimics the ploy cancer cells use to evade an immune attack, to propagate and spread. The opensource study is published in the journal Science Advances.
Previous studies show transplant patients are required to take immunosuppressant drugs for life, which weaken the immune system raising the risk of a host of infectious diseases, as well as cancer and diabetes. Therefore, an alternative approach to achieving graft acceptance through recruiting the body’s own immune system without compromising it is highly sort after. A promising hypothesis involves regulatory T cells (Treg) which are important in the regulation of immunological homeostasis. Certain tumors are known to recruit Treg cells via the release of the protein CCL22 to hide from the immune system, a property that would benefit CVA. The current study develops a synthetic microparticle system that biomimics this strategy to recruit Treg cells to use the CCL22 protein to avoid transplant rejection.
The current study engineers an artificial, controlled-release microparticle that is also fully-degradable, and capable of generating and sustaining a gradient of CCL22 ‘tumor protein’. Results show when the artificial microparticles release the CCL22 protein, the Treg cells are naturally drawn to the site of the transplantation where they tag the foreign tissue as self so it is accepted by the immune system. Data findings show the animal transplant models that had the microparticles injected twice annually maintained healthy grafts within the timeframe they were monitored, which was approximately a year.
The lab states the murine transplant models that were treated with the microparticles exhibited permanent immune tolerance to grafts, including a whole limb from a donor rat, whilst maintaining immunological homeostasis. They go on the add the ability to induce transplant acceptance without suppressing the immune system could be important in regards to VCA where patients transplants are needed to improve quality-of-life.
The team surmises they have engineered a synthetic biomimetic system that enables the cloaking and acceptance of complex VCA without compromising the immune system. For the future, the researchers state their artificial microparticle platform could have broader applications in inflammatory or autoimmune disorders where current treatments carry serious risks.
Source: University of Pittsburgh
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