ADDRESSING THE ORGAN SHORTAGE
RESEARCH & CLINICAL TRIALS
ADDRESSING THE ORGAN SHORTAGE
As an academic medical center , UAB Medicine conducts groundbreaking research as one of its missions , and at the UAB Comprehensive Transplant Institute ( CTI ), this is largely focused on solving problems for organ transplant patients . Our distinguished physician-scientists are leaders in their field , and they work closely with two main CTI labs that played key roles in UAB ’ s recent xenotransplantation breakthroughs .
The Histocompatibility & Immunogenetics Lab and the Xenotransplantation Lab perform a wide range of research and testing related to organ transplantation . These labs help improve outcomes for both allotransplantation and xenotransplantation , and they work to better understand patients ’ immune response to transplanted organs .
In September 2021 , the UAB CTI achieved a major first by transplanting genetically modified pig kidneys into a brain-dead human , as part of research that one day could overcome the worldwide organ shortage . The pig kidneys were modified with 10 key gene edits that made them suitable for direct , clinical-grade therapeutic use in humans . At the UAB CTI ’ s labs , serologic compatibility was assessed between the donor pig and the human decedent recipient prior to the transplant . These world-class labs also developed swine leukocyte antigen ( SLA ) testing protocols for this effort , and both have made important advances in the transplant field .
Paige Porrett , M . D ., Ph . D ., is the inaugural director for Vascularized Composite Allotransplantation in the UAB CTI and an associate professor in the UAB Heersink School of Medicine Department of Surgery . She emphasizes work being done at UAB to improve the methods of testing for and mitigating patient risk from infections that affect pigs , including porcine cytomegalovirus ( CMV ) and different porcine endogenous retroviruses ( PERV ), such as PERV-C . and screening procedures . We screen the pigs , but we also perform antibody testing on the recipient after transplantation . We ’ re really interested in developing serologic immune-based tests , because some viruses can be tricky and hard to detect .”
“ Obviously we want to make sure that an endogenous retrovirus doesn ’ t jump into a human host after transplant ,” Dr . Porrett continued . “ We have very good model systems that we use for experiments , because we don ’ t want to do human testing unless we actually have to , and we want to make sure that we have tested in animals to the extent that we can , for safety purposes . A lot of xenotransplant experiments in the past have used non-human primates – baboons , for example . The problem with testing for PERV is that non-human primates do not actually have the receptor that the virus likes to bind to , and this is one of the reasons why the decedent studies are so important . PERV actually integrates into the pig DNA – it ’ s hiding inside the pig ’ s own genetic code .”
Beyond disease , the donor pig and intended recipient must be tested for compatibility . As with allotransplantation , certain pigs are better donor matches for certain humans . The science in this area has come a long way in recent years , and the UAB CTI is committed to remaining on the forefront of such lifesaving developments . “ In short , before we move into really expanding xenotransplantation in humans , we must have the compatibility tests needed to safely do so .”
RESEARCH & CLINICAL TRIALS
“ Mitigating infection is something we already do in human-to-human allotransplantation , but things are a little different with pigs ,” Dr . Porrett said . “ The pigs we use as donors for xenotransplant recipients are raised in designated , pathogen-free facilities so there ’ s a very low risk of actually transmitting a disease because they undergo a variety of tests uabmedicine . org / refertransplant 5