OBJECTIVE: To observe the heart anatomic and histological structure of the Banna mini-pig inbred-lined and to provide the morphological data for heart xenotransplantation and breeding transgens pig. METHODS: Ten Banna mini-pigs (12-18 months old) were affused and fixed by common coratid artery. The heart were observed and measured by gross anatomy and histology. RESULTS: There were many similarities between the Banna pig heart and the human heart in anatomy and histology. However, the following differences were observed in the Banna pig heart: 1. Azygos vein directly drew into right atrium cordis. 2. The intercalated disk of cardiac muscle was less than that of human. 3. The Purkinje’s fibre was bigger than that of human. CONCLUSION: On the morphology and histology, the structure of Banna pig heart is similar to the heart of human being. It is possible that Banna minipig heart becomes organ donors for xenotransplantation.
【Abstract】ObjectiveTo investigate the effect of xenotransplantation of microencapsulated rabbit parathyroid tissue in different sites in rats for the treatment of hypoparathyroidism. MethodsThe parathyroid glands from Wistar rats were removed to make them aparathyroid. Ultimately, sixteen rats were included because their serum calcium values were continuously below 1.6 mmol/L. We also encapsulated the cultured rabbit parathyroid tissue with alginateBaCl2 microcapsule. According to the transplantation sites, rats were randomly divided into two groups: renal adipose microcapsule group and peritoneal microcapsule group, eight in each group. Encapsulated rabbit parathyroid tissues were then transplanted accordingly to different microcapsule groups. The calcium serum contents were examined on 5，15，25，35，45，55 and 65 d respectively after transplantation and the grafts were observed through electron microscope on the 65 d in particular. ResultsThe calcium contents after transplantation in renal adipose microcapsule group restored to normal and the observation outcomes of grafts showed that they survived well. The calcium contents of posttransplantation in peritoneal group also restored to normal with an exception that it dropped to a level lower than 1.6 mmol/L on the 65 d. Electron microscope also showed that there were necrotic tissues in the center and only a few cells survived on the edge of the grafts. Within peritoneal microcapsule group, the values were significantly lower than others taken at different phases. ConclusionMicroencapsulated rabbit parathyroid tissue that was xenotransplanted into rats can survive and function without administration of immunodepressant. There are significant differences of calcium contents at varying phases between two transplantation sites, which demonstrate that renal adipose may be an optimal site for microcapsule xenotransplantation.
OBJECTIVE To evaluate the general situation of the native pig breeds and the relative present study conditions for better development of xenotransplantation in China. METHODS By comparing the profits between the pigs and the non-human primates as the potential donors for xenotransplantation and emphasizing the source of the pigs as the organ donors from the transplantation studies, we analyzed the possible values of the native pig breeds as the donors. RESULTS As one of the richest resources in the world, the species variation and relative genetic stability of Chinese native pig breeds could be the very valuable resources for xenotransplantation study and utilization. As a reverse, the xenotransplantation could provide opportunity for more economically and environmentally utilization of the pigs besides as the meat supply. CONCLUSION As a very valuable and potential resource of organ donor, the native pig breeds of China might be noticed by the xenotransplantation colleagues in the world. It is necessary, to keep the balance among the risk vs. benefit and the protection vs. utilization of this valuable resource.
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 investigate the immunological rejection after hepatocyte transplantation for acute liver failure （ALF） in mice．Methods The hepatocytes were isolated from pig，BALB/c and C57BL/6 mice livers were conducted and then transplanted into C57BL/6 mice．CCl4 was used to make ALF mice model．The experimental animals were randomly divided into three groups， including syngenic group，allogeneic group，and xenogenic group．The survival statuses of all the mice were recorded. The alteration of T lymphocyte subsets，immune globulin，and cytokine were determined．Results ①The survival ratio was 8/10，6/10， and 3/10 in the syngenic group， allogeneic group， and xenogenic group， respectively．The survival ratio in the syngenic group was significantly higher than that in the other two groups （P＜0.05）．②The CD4+ and CD8+ T cells of the peripheral blood in the syngenic group did not change significantly on week one after transplantation．The CD4+ T cells in the allogeneic group reached the peak on day 3 after hepatocyte transplantation （P＜0.05）， while CD8+ T cells did not change much in one week．The CD4+ and CD8+ T cells in the xenogenic group increased and reached the peak on day 3 after transplantation （P＜0.05）．③There were no significantly differences of IgM and IgG in the syngenic group among 0.5， 1， and 3 d after transplantation. IgM of the allogeneic group and xenogenic group reached the peak on day 1 （P＜0.05） and IgG reached the peak on day 3 （P＜0.05） after transplantation．④The concentrations of IFN-γ， TNF-ɑ， and IL-2 in the allogeneic group and xenogenic group were significantly higher than those in the syngenic group （P＜0.05）．The concentration of IL-6 of the xenogenic group was higher than that of the other two groups （P＜0.05）. Conclusions CD4+ and CD8+ T cells play an important role in immune response to both allogeneic and xenogenic hepatocyte transplantation， as well as induce humoral immune response early after hepatocyte transplantation．
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.
After escaping from the hyperacute rejection (HAR), the xenograft has to be faced the challenge of acute vascular, acute cellular and even chronic rejection. Endothelial cells have been confirmed as a kind of antigen processing cell (APC) in allo-rejection. The porcine aortic endothelial cell (PAEC) expressed SLA-II and B7 which are the characteristics of professional APC. PAEC also has plenty of alpha-Gal residues, whether the antigen play any role in the post-HAR is still unknown. Human and porcine peripheral blood lymphocyte (PBLC) were isolated and divided into two parts, one for the effectors and the another were incubated with mitomycin C (MMC) as stimulators. The two kinds of PBLC were mixed-cultured within five days. Cultured PAEC from NJZ Pig was incubated with MMC and divided into two: One digested with alpha-galactosidase. The two kinds of PAEC were taken as stimulators to mixed-culture with human PBLC for five days. All the proliferation was detected with 3H-TdR intermingled in the system. The results showed that allo-MLR was ber than xeno-MLR in the cases. The proliferation was much ber when PAEC was used as the stimulator than that of porcine PBLC. However, the response was remarkably decreased after the digestion of alpha-Gal with alpha-galactosidase. The conclusion was that the low response of porcine-to-human MLR in vitro might be related to the predominant indirect pathway of antigen recognition in this system. While PAEC was used as the stimulator the proliferation in MLR was ber which might be concerned that PAEC itself was an APC as well as xeno-antigen sources, thus the direct pathway was predominant and worked more efficiently. The alpha-Gal might induce T cell proliferation through the linkage with the biological big molecules working as a complete antigen. The other post-HAR antigen might also exist in PAEC such as SLA-II, etc.
ObjectiveTo study the mechanism of reducing the intratumoral microvessel density (MVD) by Ginsenoside Rg3 (Rg3) combined with cytotoxic agent in xenotransplanted human breast infiltrating duct carcinoma in nude mice. MethodsSixteen female nude mice were randomly divided into 4 groups to receive cyclophosphamid (16 mg/kg,qd) combined with Rg3 (10 mg/kg, qd),Rg3(10 mg/kg,qd) alone,cyclophosphamid (16 mg/kg,qd) alone and 0.5% sodium carboxymethyl cellulose (0.5 ml,qd) respectively for 55 days. Breast cancer mass were weighed and sampled for light microscopic observation. The intratumor MVD was examined by immunohistochemical staining. ResultsThe tumor weight of treated group was significantly lower than that of control group. The tumor weight of the Rg3 combined with CTX group was lower than that of Rg3 group. The MVD value of Rg3 group was significantly lower than that of CTX group and control group. The MVD was significantly reduced in the Rg3 combined with CTX group than that in the others.ConclusionRg3 combined with CTX can inhibit the growth of xenotransplanted human breast infiltrating duct carcinoma, and reduce the intratumoral MVD.
OBJECTIVE: In the guinea pig-to-rat cardiac xenotransplantation model, the effect of complement depletion by using Chinese Cobra Venom Factor(CVF) on hyperacute rejection was evaluated. METHODS: Cardiac xenograft from guinea pig was transplanted into the abdomen of rat after the recipient being given i.p. a dose of CVF 0.20 microgram/g. the recipients were divided into group A (control group), group B (only given CVF), group C (CVF + Cytoxan + Splenectomy), group D (Cytoxan + Splenectomy) Cytoxan was injected into the abdominal cavity with a dose of 60 mg/Kg. The survival time of xenograft was measured and histologic observation was carried out after the cardiac arrest. RESULTS: The survival time of xenograft ranged from 15 to 3,120 minutes. There were significant difference among group A compared with group B and C (P lt; 0.01), and no difference between group A and group D, as well as group B and C (P gt; 0.05). There were significant difference between group B and D, as well as group C and D(P lt; 0.01). The histologic observation proved that the hyperacute rejection in group A and D was milder than group B and C. CONCLUSION: The study reveals that CVF can prolong the xenograft time by depleting complement activities and restricting hyperacute rejection in this model. Further basic and clinical study of effect of CVF in xenograft transplantation is worthwhile.
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.