International Journal of Molecular Medical Science, 2024, Vol.14, No.3, 177-192 http://medscipublisher.com/index.php/ijmms 185 In conclusion, while xenotransplantation holds great promise for addressing the organ shortage crisis, it raises complex ethical and regulatory challenges. Ensuring ethical conduct, robust regulatory oversight, and public engagement are crucial for the responsible advancement of xenotransplantation. 8 Case Studies and Clinical Trials 8.1 Analysis of successful case studies in pig-to-human xenotransplantation Recent case studies have demonstrated significant progress in pig-to-human xenotransplantation, showcasing the feasibility and initial success of genetically modified pig organs functioning in human recipients. A successful case involved the transplantation of porcine kidneys into a human decedent model, where the kidneys maintained vascular integrity and did not experience hyperacute rejection over a 74-hour period (Porrett et al., 2022). Porrett et al. (2022) reported the first use of clinical-grade genetically modified pig kidneys for xenotransplantation in a human brain-dead model. The study utilized genetically edited pigs that had certain carbohydrate antigens and complement-mediated cytotoxic reactions removed to improve transplant outcomes. The transplanted pig kidneys survived for 74 hours within the recipients, with no observed hyperacute rejection reactions. The kidneys were able to produce urine post-transplantation, though the creatinine clearance rate did not recover. Additionally, kidney biopsies showed signs of thrombotic microangiopathy, which did not worsen. The study also monitored potential transmission of porcine-derived viruses, with no transmission of porcine endogenous retroviruses detected. Through this research, the authors demonstrated the feasibility of xenotransplantation in humans and highlighted key issues that require further investigation to enhance the safety and efficacy of xenotransplantation. Figure 2 Serial histologic examination of the porcine kidney xenografts (Adopted from Porrett et al., 2022) Image caption: All biopsies represent core biopsies. (A, B, G, and H) Were obtained ex vivo. (C, D, E and F) Were obtained in vivo. Sections are stained with PASH and are 10X, except for (C and D) (40X) and (F) (silver stain). C4d negative throughout. (A and B) Mild to moderate acute tubular injury from cold ischemia. Normal appearance of the capillary network, the mesangium, and the podocytes. (C and D) Glomerulus with multiple fibrin thrombi (blue circle). There is diffuse glomerular capillary congestion with swollen endothelial cells and near complete obliteration of the peripheral capillary lumina. There is presence of fibrin thrombi and fragmented red blood cells consistent with thrombotic microangiopathy (TMA). There is evidence of progressive tubular injury with extensive acute tubular necrosis (ATN). No mesangiolysis is appreciated. (E and F) Glomerular congestion and acute tubular necrosis. Endothelial cells remain segmentally swollen with partially obliterated lumina and rare fibrin thrombi with improvement of glomerular injury. (G and H) Acute tubular injury persists. Glomeruli with segmental endothelial swelling. No fibrin thrombi (Adopted from Porrett et al., 2022)
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