Abstract
Despite recent advances in the field of transplantation, there remains a large discrepancy between the number of patients that could benefit from transplantation and the number of available donor organs. Recently, techniques for reprogramming adult cells by gene transduction to produce pluriopotent stem cells have renewed interest in the possibility of tissue regeneration for organ repair while avoiding ethical issues associated with embryonic cell use. However, this technology needs significant development before preclinical testing. Therefore, xenotransplantation of solid organs utilizing innovative gene KO swine donors as well as use of marginal donor organs with strategies to repair damaged-organ function remains at the forefront of the search for a solution to the organ shortage. Translational research utilizing relevant pre-clinical species is necessary before the powerful therapeutic implications of this murine research can be applied in a clinical setting. CLAWN miniature swine that have been developed in Kagoshima University, were MHC inbred miniature swine. The preclinical large animals were particularly useful in assessing the effects of MHC matching on rejection and／or tolerance induction. Our research laboratory, Organ Replacement and Xenotransplantation Surgery, Advanced Biomedical Science and Swine Research, Kagoshima University, aims to develop innovative strategies to overcome organ shortages in preclinical large animal models；(1)xenotransplantation in GalT-KO pigs to non-human primates,(2)allotransplantaton, kidneys, lungs, islets and small intestine in MHC inbred CLAWN miniature swine and (3)ischemic reperfusion(IRI)models in CLAWN miniature swine. In this lecture, we introduce our recent data, especially focus on(1)preclinical IRI lung／kidney models and(2)recent attempts to reduce／inhibit IRI with CO inhalation or anti-HMGB1 antibody in CLWAN miniature swine.
