OBJECTIVE: To investigate the role of direct and indirect recognition in pig-to-man xenotransplantation. METHODS: Taken the peripheral blood lymphocytes (PBLC) from three Neijiang pigs and two humans as stimulators and respondors, the one-way mixed lymphatic reactions (MLR) of xenograft were carried out, and allo- and self-PBLC as control. RESULTS: Among the three patterns of MLR, syngeneic was MLR the lowest in proliferation, the allogenic MLR was the highest, and the xenogenic MLR was medium. The PBLCs from humans and pigs were matched on HLA-A, B, DR and DQ by means of modified Terasaki assay. The match on pigs was failure because of the pre-existing natural xenogenic antibody in the testing serum. CONCLUSION: The results suggest that the degree of MHC matching still affect the rejection in xenotransplantation, but the present serum assay of MHC matching is not fit for pig.
The worldwide shortage in the supply of donor organs and tissues is becoming more pronounced. Xenotransplantation may probably give the hope to overcome the problem ultimately. However, it gives rise to a number of social and ethical issues, among them, the pig appears to be a likely source for human transplantation because it entails least social and ethical issues than no-human primates or other animals and the pig is similar to human in many aspects. The ethical and economic aspects must also be taken into consideration. Patient and his family’s privacy may be stripped because the patient has received a new or unusual treatment. Xenograftings will squint towards a kind of commodities which are different from human graftings and it is a challenge to human transplantation. Xenotransplantation brings a risk of creating new human disease and pandemic, so, it is necessary to formulate a policy and provide input to draft guidelines on the regulation of xenotransplantation.
OBJECTIVE To detect the immunoreaction after osteoblast xenotransplantation and to investigate the possibility of heterogenic osteocyte transplantation and tissue engineered bone reconstruction. METHODS: Rat osteoblasts were isolated by two-part bony digestion/elements in culturing, and incubated in vitro at 37 degrees C, 5% carbon dioxide for 5 days until they multiplied and formed a monolayer on the bottom of dish. Twenty-eight rabbits were divided into 3 groups. Autograft of osteoblasts(group A), xenograft of osteoblasts(group B) and normal saline(group C) were implanted into the rectus abdominus muscle. The immunological and histological observations were performed after 1, 2, 4 and 8 weeks of transplantation. RESULTS: Cultured cells reached confluence within 5 days and was identified as osteoblasts by ALP staining and Bon kossa staining. The result of host versus graft reaction was negative. In group B, specific antibody reaction was detected 2 weeks and 4 weeks after transplantation. Cell mediated cytotoxicity was detected after 2 weeks, reached the peak value 4 weeks later, and then began to decline 8 weeks later. HE staining showed mass inflammatory cells and no ectopic ossification after 8 weeks. CONCLUSION: Heterogenic osteoblast transplantation will lead to an obvious change in host humoral and cellular immunity and lost the ability of bone formation. So, it can not be used for the reliable cell sources for osteocyte transplantation or tissue-engineering bone reconstruction.
OBJECTIVE: To explore the kidney anatomic structure of banna minipig inbred-lines, and to provide data for kidney xenotransplantation. METHODS: The fresh and infused kidneys of banna minipig (including the vessel and the ureter) were checked by anatomic microscope and vernier caliper in original location and away body. The tissue structure was observed by HE stain. RESULTS: The structure of kidney of banna minipig inbred-lines (including the vessel and the ureter) are similar to that of human being. The fascia propria of kidney is divided into three layers including capsula fibrosa, capsula adipose and fascia renalis. The thickness of cortex renalis is (20.0 +/- 2.4) mm. The average diameter of renal artery is 5.1 mm and is similar to that of human being. All the kidneys of banna minipig inbred-lines have a single branch renal artery. The diameters of left and right ureters are 5.1 mm and 4.7 mm, respectively. CONCLUSION: The kidney of banna minipig inbred-lines is an ideal replacement of human kidney for xenotransplantation.
Objective To improve the Heron’s technique for heterotopic cardiac transplantation in rats by cuff vessel anastomosis in some aspectsand successfully establish the simplified model of cervical cardiac xenotransplantation from guinea pigs donor to SD rats recipients. Methods The donors were 64 male guinea pigs, whose weight ranged from 250 to 350 g； the recipients were 64 male SD rats, whose weight ranged from 300 to 350 g.The guinea pigs donor’s ascending aorta and pulmonary artery were anastomosed to SD rats recipient’s right common carotid artery and external jugular vein respectively with a self-made “sleeve” anastomosis. The modified cuff technique of heterotopic grafting is described in detail. Results 64 consecutive successful transplantations have been performed by single surgeon were done with negligible operative risk. No anastomosis leakage nor vessel obstruction. The total time of surgical procedure were 45 to 60 minutes. The new technique allowed vascular anastomoses to be completed in 2 to 5 minutes. The total cold ischemia time for donor heart was 14 minutes in average. Conclusion This modified Heron’s technique was a simple, economical, practicable,reliable and high reproducible model can be operated by surgeons with minimal training in microvascular surgery, and be applied to various transplantation immunological studies.
Objective To evaluate tissue regeneration, body reaction, and biological safety of xenogeneous bladder acellular matrix (BAM) that can be used to repair rabbit bladder. Methods Porcine BAM was prepared through physical, chemical, and enzymatic methods, and the effects of acellularization and the structure were observed with HE staining and scanning electron microscope (SEM). Eighteen New Zealand white rabbits (weighing, 2.5-3.0 kg) undergoing partial cystectomy were randomly divided into 2 groups. After partial (about 30%) cystectomy, the porcine BAM was used to replace partial rabbit bladder in the experimental group (n=12), and the incision was directly sutured as control group (n=6). The survival condition of animals was observed after operation. At 15 days, 1, 2, 3, and 6 months after operation, the blood routine, renal function, and electrolyte were tested by collecting the blood samples. At 1, 2, 3, and 6 months after operation, maximum bladder capacity, bladder leak point pressure, and bladder compliance were measured through urodynamic studies. Then gross observation was performed for regeneration of bladder, and the specimens of the bladder were harvested for HE staining and immunohistochemical staining. The surrounding organs and local lymphoid tissues were harvested for gross observation and HE staining. Results Cell components were completely removed in the porcine BAM, showing three-dimensional porous structure under SEM. All the animals survived during the experiment. At 15 days after operation, white blood cell count increased, and then returned to normal level in 2 groups, showing no significant difference between 2 groups (P gt; 0.05). The tests of renal function and electrolyte suggested no significant difference between 2 groups (P gt; 0.05). The level of serum creatinine showed a tendency of increase, but it remained within normal range at 6 months after operation. The maximum bladder capacity and compliance in experimental group were significantly higher than those in control group at 3 and 6 months after operation (P lt; 0.05), but no significant difference in bladder leak point pressure at each time point between 2 groups (P gt; 0.05). The urothelial regeneration, smooth muscle regeneration, and blood vessel regeneration were seen by histological observation in 2 groups. In the 2 groups, chronic inflammatory cells infiltration could be observed at 1 month postoperatively, and then chronic inflammatory cells decreased significantly (P lt; 0.05), until complete disappearance. There was no significant difference in score of chronic inflammatory cell infiltration between 2 groups at 3 and 6 months after operation (P gt; 0.05). The α-smooth muscle actin expression was significantly increased with time passing in 2 groups (P lt; 0.05), and it was significantly higher in control group than in experimental group at each time point (P lt; 0.05). In addition, gross and HE staining observations showed no abnormalities in surrounding organs and local lymphoid tissues. Conclusion No immune rejection response occurs when porcine BAM is used for xenotransplantation. It is indicated that porcine BAM is relative safety for xenotransplantation.
OBJECTIVE: To evaluate the histological characteristics of xenogeneic graft-versus-host disease (GVHD), and to differentiate it from the allogeneic GVHD. METHODS: The original articles related to the characteristics of xenogeneic GVHD and the relationship between xenogeneic GVHD and allogeneic GVHD were widely reviewed in the past decade. RESULTS: Xenogeneic GVHD was different from allogeneic GVHD in the speed of development, position and features of pathological changes, due to the incompatibility of common simulative signals, adhesive molecules and difference of antigens. Xenogeneic spleen transplantation could induce xenogeneic GVHD. CONCLUSION: Xenogeneic GVHD can be used as a model to mimic rejection in xenotransplantation and to evaluate the compatibility of xenotransplantation.
Objective To summarize the research progress of xenotransplantation.Methods Domestic and international publications about xenotransplantation were summarized and reviewed. Results Hyperacute xenograft rejection was a huge problem for xenotransplantation， but it could be alleviated if the organs or tissues of donor were genetically modified. So far the graft survival time differed greatly due to characteristics of different organ. Conclusions By reviewing the studies of relevant papers about xenotransplantation， a comprehensive understanding of research background and a suitable research direction of xenotransplantation can be supplied. The graft organs or tissues from genetically modified donors are expected to avoid or alleviate hyperacute xenograft rejection.
OBJECTIVE To investigate the mechanism of xenotransplantation rejection and the interaction between the immunocytes. METHODS: This review concluded the research achievements and new advances in xenotransplantation based on the relevant experimental data. RESULTS: Transgenic pig technology and novel immunosuppressants were applied to suppress hyperacute rejection and acute vascular rejection respectively. Modulation of T cell and antigen presenting cells and induction of tolerance were taken for the prevention of acute cellular rejection. CONCLUSION: In general, the technology of transgenic pig is relatively mature and effective. The mechanism and prevention of acute vascular rejection and acute cellular rejection should be further investigated.
Objective To review the current condition, test method and progress of the animal model of xeno graft versus host disease(xeno GVHD). Methods The literature review and comprehensive analysis methods were used in this article. Results Implanted immunologic cells, the recepient had the chance of showing host versus graft reaction, GVHD or microchimerism. Now, xeno GVHD could be induced in vivo at small and large animals, it also could be supervised through many ways. Conclusion Chimeric cell is very important to xeno-GVHD animal model. With this model, we can really mimic the immunologic change in vivo after xenotransplantation.