Limitation of donor source for allograft makes the research on xenograft progress. Pig is regarded as one of the ideal donor animals. The major obstacle in xenograft is hyperacute rejection, which is caused by complements after they are activated by xenogeneic antigens combined with natural antibodies. It has been confirmed that alpha-Gal is the major target antigen, whose expression is incharged by alpha-1,3 galactosyltransferase (alpha-GT). The approaches to overcome hyperacute rejection against alpha-Gal included: immunoadsorption of xenogeneic natural antibodies, lysis of antigen by enzyme and genetic manupilation to obtain animal lack of alpha-GT. Besides alpha-Gal, there were other antigens binding to human serum antibody, such as gp65 and gp100, which was expressed on PAEC after induced by TNF, the A-like antigen. But their function was still unknown. It was debatable on the role of MHC in xenograft. Both direct and indirect pathway were involved in cellular response in xenograft.
Objective To establ ish the modified model of cervical heterotopic cardiac transplantation in rats for investigation of cardiac chronic rejection. Methods Forty healthy male Wistar rats, aged 10 weeks, weighing 250-300 g, were appl ied as the donor group, and forty healthy male SD rats, aged 10 weeks, weighing 300-350 g, served as the recipient group. The donors’ pulmonary artery was anastomosed to the reci pients’ right external jugular vein by non-suture cuff technique while the donors’ innominate artery was anastomosed to the recipients’ right common carotid artery by suture microvascular anastomosis. All recipients received cyclosporin to prevent acute allograft rejection. Results Forty consecutive successful transplantations were performed. Neither anastomosis leakage nor vessel obstruction occurred. The total operation time was 40-50 minutes. The time of cuff vascular anastomosis was 2-3 minutes and that of microvascular anastomosis was 9-12 minutes. All recipients survived for more than 30 days and all allografts were examined at 30 days after the transplantation. Pathological manifestations of allograft vessels were chronic rejection. Conclusion This modified model of cervical heterotopic cardiac transplantation is simple, practical and highly reproducible and is appl icable for investigation of chronic rejection in various organ transplantation studies.
Insufficient supply of organ for allotransplantation made the study on finding new organ resources from animal progress. Pig is regarded as one of the optimal donor animals for human. The major obstacle in this field is hyperacute reaction (HAR), which is triggered after the xenogenic natural antibodies preexisting in recipient blood combine to the antigens on the surface of the endothelium and activate the complement system. alpha-Galactose residues (alpha-Gal) on the endothelial cell have been identified as the major xenoantigens. NJZ Pig has been closely breed since 1938, whose family history is clear. Tissue samples from heart, liver, kidney, pancreas, lung, small intestine, skin, spleen, thymus and lymph node were obtained and embedded in paraffin. The sections were performed the immunohistochemical staining with the sera from health volunteers (including all the blood types) as the primary antibodies as well as the biotin labeled bandeirae simplicifolia I isolectin B4 (BS I-B4), which has specific affinity to alpha-galactose. All the staining sections were compared with the tissues digested with alpha-galactosidase. There was no difference between the antigens recognized by sera of different blood types. alpha-Gal was still the major xenoantigen on the endothelial cells. There might exist non-alpha-Gal antigens on the distal convoluted tubules and collecting tubules of the kidney. There was no alpha-Gal distributing on the secreting part of pancreas, either the islet cells or the matrix cells, but surely on pancreatic duct and vessels. All the antigenity was destroyed after the enzyme digestion except that the small intestine gland still positive with the BS I-B4. alpha-Gal is the major xenogenic antigen in NJZ Pigs. There exist some unknown antigens on the distal convoluted tubules and collecting ducts of the kidney. The blood type of recipient is not the first affair to be considered in pig-to-human xenotransplantation. The specificity of BS I-B4 for the alpha-galactose needs more detail research.
ObjectiveTo explore apoptosis of acinar cells during pancreatic allograft rejection in rats.MethodsGroups of Wistar rats underwent heterotopic pancreaticoduodenal transplantation from syngenic Wistar of allogenic SD rats. The grafts were harvested on postoperative day 3, 5 and 7. All graft samples were subjected to histological examination and apoptotic cells of graft acinar cells using in situ terminal deoxynucleotidy1 transferasemediated dUTP nickend labeling (TUNEL). Histopathological rejection score and apoptotic index (AI) were analyzed. ResultsThe incidence of apoptotic cells was increased steadily over time in allografts, in contrast with syngenic grafts. The apoptotic cells in allografts were mainly acinar cells and few infiltrating lymphocytes. A significant correlation between apoptotic index and histopathological rejection score was noted.ConclusionTUNEL can display apoptosis of single cell in situ. Apoptosis is an important mechanism of tissue injury in acute pancreatic allograft rejection in rats. Acinar cell apoptosis can be used as a valuble index to estimate the injury of grafts and to monitor the acute rejection.
Objective To evaluate the long-term function of the traumaticallydamaged joint after its repair with transplantation of a fresh or a frozen allogenic joint. Methods From March 1977 to September 1993, 13 patients (9 males, 4females; age, 17-55 years) with traumatically-damaged joints underwent transplantation of the fresh or the frozen allogenic joints. Five patients had 5 damagedmetacarpophalangeal joints, 6 patients had 9 damaged interphalangeal joints, and 2 patients had 2 damaged elbow joints. So, the traumatic damage involved 13 patients and 16 joints. All the metacarpophalangeal joints and the interphalangeal joints were injured by machines and the 2 elbow joints were injured by road accidents. The patients were randomly divided into 2 groups: Group A (n=7) andGroup B (n=6). The 7patients with 8 joints in Group A underwent transplantation of fresh allogenic joints; the 6 patients with 8 joints in Group B underwent transplantation of frozen allogenic joints. The allogenic joint transplants were performed in the period from immediately after the injuries to 6 months after the injuries. The motion ranges of the transplanted joints and the X-ray films were examined after operation, and the immunological examination was performed at 8 weeksafter operation. Results The time for synostosis was 5-8 months in Group A, but4-6 months in Group B. In Group A, at 2 years after operation the metacarpophalangeal flexion was 30-40° and the interphalangeal flexion was 20-30°; however,at 6 or 7 years after operation the interphalangeal flexion was only 10-20°. The patients undergoing the transplantation with fresh elbow joints had the elbowflexion of 60° and the elbow extension of 0°, and had the forearm pronation of 30°and the forearm supination of 30°. But in Group B, at 2 years after operation the metacarpophalangeal flexion was 6070° and the interphalangeal flexionwas 40-50°; at 6 or 7 years after operation the interphalangeal flexion was still 40-50°. However, the patients undergoing the transplantation with frozen elbow joints had the elbow flexion of 90° and the elbow extension of 0°, and hadthe forearm pronation of 45° and a forearm supination of 45°. The joint motion ranges, the Xray findings, and the immunological results in the patients undergoing the transplantation of the frozen allogenic joints were significantly better than those in the patients undergoing the transplantation of fresh allogenicjoints. There was a significant difference in the immunological examination between Group A and Group B (IL2, 21.64±3.99；CD4/CD8,3.88±0.82 vs.IL-2,16.63±3.11；CD4/CD8, 2.53±0.23, P＜0.01). Conclusion Repairing the traumatically-damaged joints with frozen allogenic joints is a better method of regaining the contour, movement, and complex motion of the hands.
ObjectiveTo summarize the advances of precl inical research in xenogeneic (porcine) cell transplantation in recent years. MethodsThe literature about the precl inical research in xenogeneic (porcine) cell transplantation was analyzed and summarized. ResultsWith the application of new immunosuppressive agents and the generation of transgenic pigs, great progress has been achieved in xenogeneic transplantation of pig-derived nerve cells, islet cells, liver cells, and various types of stem cells. The survival time of xenogeneic cell (porcine) significantly prolonged, but there is still a long way to go before cl inical application. ConclusionThe source of xenogeneic (porcine) cells is abundant and the experiments are reproducible. However, how to effectively prevent rejection and prolong the survival time in the host, and avoid the spread of virus between species are still need to be solved in the future research.
Objective To observe the expression of heat shock protein 70 (HSP70) in human liver after hepatic transplantation, and to study its correlation with the occurrence and progression of acute allograft rejection.Methods Fifteen biopsy specimen of allograft liver after transplantation were collected and divided into three groups according to their pathological changes: control group (no rejection), mild acute rejection group, and moderate/serious acute rejection group. The expressions of HSP70 in grafts were detected by using immunohistochemical method and imaging analysis. Results HSP70 was expressed in all 3 groups, and appeared mainly in hepatocellular cytoplasm. The immunohistochemical imaging analysis of HSP70 showed: integral optical density (IOD) which was 30.99±11.14 in the control group was lower than that in the mild acute rejection group (68.84±21.37) and that in the moderate/serious acute rejection group (71.82±19.99), P＜0.01； and the IOD in the moderate/serious acute rejection group was higher than that in the mild acute rejection group (P＜0.05). Conclusion HSP70 plays a role in cellular protection for allograft liver, and the continuously increasing expression of HSP70 in graft maybe closely relates to the occurrence and progression of acute allograft rejection.
Objective Ｔo summarize the advancement of ABO-incompatible liver transplantation. Methods Relevant literatures about ABO-incompatible liver transplantation, which were published recently domestic and abroad were reviewed and analyzed. Results Owing to various treatments recent years, outcomes of ABO-incompatible liver transplantation have been improved dramatically. Conclusion With effective immnosuppressive protocols and effective perioperative management, ABO-incompatible liver transplantation is feasible.
Objective To investigate the mechanism of hyperacute rejection (HAR) in pig to rhesus monkey vein xenograft. Methods Porcine femoral vein was transplanted into rhesus monkey. Deposits of IgM, IgG, C3 and C4 on the grafts were observed by immunoflurescence. Results Great deal of IgM, C3 and C4 were seen along the endothelium of donor vein, but IgG was not seen. ConclusionIn pig to monkey xenograft model, HAR is intiated by the binding of xenoreactive IgM to donor xenoantigens and followed by the activation of complement via the classical pathway.
PURPOSE:To carry out preliminary study on immunogenicity or'the retina and provide theoretical bassis of transplant rejection of the retina. METHODS:The allogeneic whole retinal or photoreceptor layer from C57BL/6 mice wer transplanted subcutaneously into BALB/C mice for antigen exposure and delayed hypersensitivity (DH) and modified 51Cr-release assay for specific cytotoxic T lymphoeytes (CTL)were emploied. RESULTS:The allogeneic whole retinal transplantation gave rise to DH(Plt;0.05 )and increased function of CTL of which the killing rate was 33.4% in concentration of 1:90 comparing with negative group (4.8% in 1:90,Plt;0.05)and the risen function could be blocked by anti-CD8. CONCLUSION:We deduce that allogeneic whole retina has immunogenicity and should pay attention to transplant rejection postoperatively.but the photoreceptor layer seems to have no immunogenicity and may be no transplant rejection after its transplantation. （Chin J Ocul Fundus Dis,1997,13: 234-236）