International Journal of Molecular Medical Science, 2024, Vol.14, No.3, 177-192 http://medscipublisher.com/index.php/ijmms 187 Figure 3 Photographs of the Thymokidney in Situ (Adopted from Montgomery et al., 2022) Image caption: Panel A shows the thymokidney just after reperfusion in Recipient 1; the ureter is on the right side. Panel B shows the thymokidney in Recipient 1 at 54 hours just after reperfusion; the thymokidney was pink and viable without outward signs of ischemia or infarction. Panel C shows the thymokidney immediately after reperfusion in Recipient 2, and Panel D shows the kidney at 54 hours. Panel E shows the setup of the ureter connection to the gravity drainage system (to isolate the urine obtained from the thymokidney) and the plastic silo (Adopted from Montgomery et al., 2022) 8.3 Outcomes and lessons learned from clinical applications The outcomes of initial clinical applications of pig-to-human xenotransplantation have provided valuable insights into the challenges and potential of this technology. One significant lesson is the importance of selecting appropriate genetic modifications to address specific immunological barriers. For example, the expression of human thrombomodulin in genetically modified pigs has been shown to prevent intracardiac thrombus formation in pig-to-baboon cardiac xenotransplantation models, indicating its potential benefit in human trials (Goerlich et al., 2020). Additionally, the need for rigorous immunosuppressive protocols and continuous monitoring to prevent rejection and manage complications has been emphasized in these studies. Overall, these case studies and clinical trials highlight the progress made in xenotransplantation and the critical role of genetic modifications in overcoming immunological challenges. Continued research and clinical testing will be essential to further refine these techniques and improve the long-term success of pig-to-human organ transplants. 9 Challenges and Future Directions 9.1 Technical challenges in achieving long-term graft survival Achieving long-term graft survival in pig-to-human xenotransplantation involves addressing several technical challenges. One of the primary hurdles is overcoming hyperacute rejection, which can occur minutes to hours after transplantation due to the presence of preformed antibodies in the recipient that recognize pig antigens. Advanced genetic modifications, such as the knockout of the alpha-Gal gene, have been critical in reducing this risk. However, other forms of rejection, including acute vascular and cellular rejection, still pose significant
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