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Georgia Tech researchers have developed a sophisticated nanoparticle that can alert clinicians to the early stages of immune rejection of transplanted organs through a simple urine test. Nanoparticles can accumulate in transplanted organs and detect immune rejection. They then release molecules that fluoresce the urine of the recipient organ. With the help of a simple urine test, clinicians can then badess whether an organ rejection occurs, potentially replacing the need for invasive biopsies.
Organ transplantation gives new life to organ recipients, but it is not without risk and without complications. One of the most serious is immune rejection. At the present time, it is difficult to determine whether immune rejection occurs early in the process. Often, clinicians do not realize that this has happened before significant organ damage has already occurred. Organ biopsies are at risk and invasive, and often do not indicate whether early immune rejection occurs.
"The biopsy is not predictive. It's a static snapshot. It's like looking at a picture of people jumping, "says Gabe Kwong, a researcher involved in the study. "You do not know if they go up or down. With a biopsy, you do not know if the rejection is progressing or regressing. "
Identifying early immune rejection and monitoring the immune response over time could allow clinicians to change the dose of immunosuppressants that a person receives, to prevent or reduce organ damage . To achieve this, Georgia Tech researchers have developed a new type of nanoparticle that is delivered intravenously and can accumulate in transplanted organs.
The particles consist of an iron oxide core coated with amino acid hairs whose ends are endowed with fluorescent molecules. When T cells release a specific enzyme involved in the early stages of immune rejection in the vicinity of a nanoparticle, it cuts the bristles and releases the fluorescent molecules, which pbad through the bloodstream and end up in the urine.
Until now, researchers have tested the system in mice that received a small skin graft. Early-stage immune rejection meant that the animal's urine shone, facilitating detection and monitoring over time through a simple urine test. This test could allow clinicians to accurately adjust the dose of immunosuppressants to control the immune response.
"The dose adjustment is very difficult but very important because a significant immunodeficiency increases the occurrence of infections and the patients who receive it also have cancer more often," Kwong said.
Image: A T cell, here in purple, comes into contact with a grafted organ cell, here in brown and purple. The T cell secretes the granzyme B enzyme, here in gray, which attacks the organic cell. But granzyme B also separates fluorescent signal molecules, in green, from the rejection detection nanoparticle, in bright red. The signal molecules make their way into the urine, where they emit a fluorescent signal.
Study in Nature Biomedical Engineering: Early noninvasive detection of acute rejection of a graft via nanosensors of granzyme activity B …
Georgia Tech …
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