Checking xenografts
Prediction of graft rejection using artificial blood vessels
Anna Yudina, "Scientific Russia"
Scientists are developing a platform that can evaluate immune responses using human blood. Such a platform will find application in the field of transplantation, – writes eurekalert.org .
Organ transplantation involves organ transplantation from donors as a means of treating diseases or injuries, but there is a shortage of organs available for donation compared to the demand for organ transplantation. Research related to animal organ transplantation (xenotransplantation) continues, given their potential to overcome these problems. Heart valves and the cornea of pigs, in particular, are used for treatment involving xenotransplantation. They cannot tolerate tuberculosis and AIDS, which can appear during organ transplantation from monkeys. Pigs also have the advantage of low cost due to mass production.
However, an immune rejection reaction that destroys the transplanted tissue can occur in the human body after xenotransplantation. Attempts are being made to overcome this problem by breeding pigs specifically for xenotransplantation by genetic manipulation of various factors causing immune rejection. However, such development was postponed due to limitations in the methods used to test the suitability of the developed pig organs for the human body.
The Korea Institute of Science and Technology (KIST) announced that a research group led by Yangmi Jung from the Biomaterials Research Center, together with a research group led by Jae-seok Yang, a professor at the Seoul National University Organ Transplantation Center, has developed a bio–artificial blood vessel. This blood vessel simulates the function and properties of human blood vessels to test the success of xenotransplantation, along with a vascular circulatory platform that reproduces the human circulatory system.
A drawing from an article by Kim et al. Tissue-engineered vascular microphysiological platform to study immune modulation of xenograft rejection, published in the journal Science Advances –VM.
Usually, the immune rejection reaction that occurs after transplantation of an artificial organ or medical device involves blood thickening and blockage of blood vessels caused by blood clotting when the blood vessels of the organ and the recipient are connected. Currently, it is impossible to know in advance whether an organ transplant will be successful to a human or a recipient animal. In particular, there is no other way to examine blood clotting, except in an environment similar to a blood vessel through which blood actually flows.
To test for blood clotting before transplantation, Jung developed an artificial blood vessel using a simple process of pouring liquid hydrogel into a tubular mold made of collagen and fibrin, the main components of blood vessels, and then solidifying it at 37°C with compression. This ensures blood circulation, both in terms of actual blood flow and blood pressure. While the structure of existing artificial blood vessels requires the cultivation of vascular endothelial cells for 7-21 days, this new artificial blood vessel allows the production of blood vessels in less than 3 days due to the stable attachment of vascular endothelial cells. This method, used as an analytical tool, significantly reduces the duration of experiments.
The artificial blood vessel platform developed by Young's research group has been tested not only in in vitro experiments, but also in vivo experiments on animal models. The research team cultured genetically modified pig vascular endothelial cells on the endothelium of the vascular platform to create an artificial pig blood vessel, after which a test was performed for human blood circulation through the blood vessel in vitro. An in vivo experiment was also conducted using mouse models with transplanted pig blood vessels to simulate the human immune response. After evaluating the immune rejection reactions observed in both in vivo and in vitro experiments, it was demonstrated that a blood vessel sample developed by the research team using a specially engineered gene effectively suppressed acute immune rejection. This demonstrated the potential of the genetically modified pig developed in this study to be used as a donor animal with a low level of immune rejection.
According to Jung, "the artificial blood vessel platform is not only structurally similar to real blood vessels, but also mimics the physical and biological properties of blood vessels, creating a microenvironment similar to the human circulatory system," and can "be used as a preclinical tool for screening new drugs and immunotherapeutic agents in corporations and hospitals, demonstrating their commercial usefulness".
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