猪内源性反转录病毒与异种移植的安全性

人们已成功地将猪心脏瓣膜移植入人体内 ,猪皮肤已作为烧伤患者的暂时覆盖物 ,猪胰岛细胞已被植入糖尿病患者体内 ,异种移植已展现出十分诱人的前景。但猪→人异种移植主要存在三方面的问题 :( 1)免疫排斥反应 ,包括超急性排斥反应 (ＨＡＲ)、延迟性异种移植排斥反应 (ＤＸＲ)、Ｔ细胞介导的排斥反应 (ＴＭＲ) ;( 2 )猪→人生物学组分的相容性 ;( 3)种间交叉感染病毒的安全性。尤其令人关注的是潜在性和内源性反转录病毒的生物安全性。自上世纪 90年代以来 ,由于对异种移植超急性排斥反应的发生机理有了更深入的研究 ,也有赖于分子生物学、…     

异种移植与中国地方猪种资源的利用

目的了解中国地方猪种资源概况及研究现状,使之更好地为异种移植服务。方法通过比较猪与非人灵长类动物在异种移植上的优劣及当前异种移植界对猪种资源的重视,分析中国地方猪种在异种移植供体选择上是否存在优势。结果中国是猪种资源最丰富的国家之一,猪种多样性和遗传相对稳定性为异种移植提供了可贵的研究和利用资源,而异种移植又为猪种的利用提供了机遇。结论中国地方猪种资源可能会引起世界异种移植界的重视,在其保护与利用、风险与利益间找到平衡点是必要的     

猪到猕猴异种心脏移植超急性排斥反应的免疫学及病理学变化

目的观察猪到猕猴异种心脏移植超急性排斥反应时的免疫学及病理学变化。方法采用猪到猕猴腹腔内异位心脏移植模型,检测发生超急性排斥反应者的血液中补体、天然抗体及T淋巴细胞亚群的变化,并对移植心脏进行免疫组化(测定C3、C4、C5b9、IgG及IgM的沉积)及病理学分析。结果发生超急性排斥反应时,血清补体C3、C4的含量、总补体活性及抗猪内皮细胞天然抗体均有一定程度的下降;CD4 /CD8 T淋巴细胞的比率也有所下降;移植心脏中均有补体C3、C4、C5b9的沉积,IgG及IgM也均有沉积,但IgG和IgM沉积强度的差异无统计学意义;病理学改变主要为心肌间质弥漫性出血、水肿,毛细血管内普遍淤血。结论补体通过经典途径激活参与猪到猕猴异种心脏移植超急性排斥反应;超急性排斥反应时受者血中天然抗体水平明显下降;CD4 T淋巴细胞可能参与异种移植超急性排斥反应过程并有所消耗;发生超急性排斥反应的移植物突出病理表现为间质出血。     

GGTA1基因敲除猪胰岛细胞移植到Ⅰ型糖尿病猕猴3例报道

目的 探索GGTA1基因敲除猪胰岛细胞移植到Ⅰ型糖尿病猴的效果.方法 本研究采用GGTA1基因敲除新生猪胰岛细胞开展了3例猪-猴异种胰岛移植实验.结果 3只猕猴成功进行胰岛细胞移植治疗,术后生命体征平稳,未发生静脉栓塞症状.移植后血糖和外源胰岛素用量均显著降低,能检测到特异性猪C肽.移植后3只猕猴均发生了酮症酸中毒症状...     

肝细胞移植治疗急性肝功能衰竭的免疫排斥研究

目的研究肝细胞腹腔移植治疗急性肝功能衰竭的免疫排斥反应。方法用胶原酶灌注法分离幼猪及BALB/c和C57BL/6小鼠肝细胞;用腹腔注射CCl4的方法建立C57BL/6急性肝功能衰竭模型;将实验动物分为同基因移植组、同种异基因移植组和异种移植组。各组动物肝细胞移植入急性肝功能衰竭小鼠腹腔内,观察受体小鼠存活情况,比较各组动物T细胞亚群、免疫球蛋白水平和细胞因子的变化。结果①受体小鼠存活情况:同基因移植组为8/10,同种异基因移植组为6/10,异种移植组为3/10,同基因移植组和同种异基因移植组受体的生存情况明显好于异种移植组(P<0.05)。②T细胞亚群变化:移植后7 d内,同基因移植组外周血中CD4+和CD8+T细胞均无明显变化,同种异基因移植组CD4+T细胞于移植后3 d时达高峰(P<0.05),而CD8+T细胞7 d内无明显变化,异种移植组CD4+和CD8+T细胞移植后7 d内均明显升高,且于移植后3 d时达高峰(P<0.05)。③免疫球蛋白水平:同基因移植组血清免疫球蛋白IgM和IgG水平在移植后0.5、1和3 d时未见明显变化,同种异基因移植组和异种移植组的IgM在移植后1 d时达高峰(P<0.05),而IgG在移植后3 d时达高峰(P<0.05)。④血清细胞因子水平:移植后7 d,同种异基因移植组和异种移植组的IFN-γ、TNF-α及IL-2血清浓度明显高于同基因移植组(P<0.05);异种移植组的IL-6血清浓度明显高于同基因移植组和同种异基因移植组(P<0.05)。结论无论同种还是异种肝细胞移植,初期均发生了强烈的CD4+及CD8+T细胞参与的细胞免疫和较强体液免疫反应。     

异种移植免疫排斥的研究进展

异种移植是解决人体器官严重短缺的重要思路.随着对异种移植排斥和人畜共患感染性疾病的深入研究,以及α-1,3-半乳糖苷转移酶基因敲除猪的成功构建,以猪为供体的异种移植与临床应用之间的距离正在逐渐缩短.阻碍异种移植发展的主要障碍仍是免疫排斥反应.本文试就目前异种免疫排斥的研究进展进行综述,希望对未来的临床异种移植研究提供参...     

补体在猪到猴异种心脏移植中的作用及机理

目的 探讨补体在异种大动物猪到猴心脏移植排斥反应中的作用及机理.方法 以梅山猪为供者,中国猕猴为受者,行异种腹腔异位心脏移植.随机将受者分为3组.A组(5只):为空白对照组,受者心脏移植后不作任何处理.B组(5只):为照射预处理组,受者于心脏移植前28 d、即1.5个月龄时接受60Coγ3 Gy全身剂量照射,其余同A组.C组(8只):为照射+胸腺注射预处理组,心脏移植前21 d,将供者的脾细胞(按照5×107个/只的数量)注入受者的两侧胸腺内,其余同B组.观察心脏移植术后各组移植心的存活时间;猪对猴单向混合淋巴细胞培养的刺激效应;采用双抗体夹心法检测补体C3和CD46的血清浓度;通过流式细胞术检测受者外周血细胞表面IgM、IgG阳性细胞百分比水平.结果 A、B、C三组移植心的存活时间分别为:(36.6±5.8)h、(65.6±6.5)h和(91.1±22.8)h,C组移植心的存活时间明显延长,与A组比较,P＜0.01,与B组比较,P＜0.05.C组在猪对猴单向混合淋巴细胞反应中的刺激效应较A、B组明显下降(P＜0.01).B、C组移植前补体水平(C3)无明显变化,但随着IgM、IgG水平的上升,发生排斥反应时C3和CD46水平显著降低.C组猕猴特异性抗猪抗体IgM及IgG的上升速度均较A、B组明显延缓.结论 对受者进行异种胸腺注射联合全身照射预处理在抑制T淋巴细胞免疫及体液免疫方面有重要作用,但无法抑制异种排斥反应中补体的激活,补体通过经典途径参与了延迟性异种排斥反应的发生.     

猪到人异种移植超急性排斥反应的靶抗原

目的　探索猪到人异种移植超急性排斥反应的靶抗原。方法　对近年来国内、外有关文献进行检索 ,并作综述。结果　α半乳糖基 (α Gal)是目前公认的猪到人异种移植超急性排斥反应的主要抗原 ,其表达受α 1,3半乳糖转移酶 (α 1,3GT)控制。克服α Gal引起的超急性排斥反应的方法有免疫吸附天然抗体、酶消化α Gal、α GT基因敲除及转基因技术等。除α Gal外 ,还存在与人血清中天然抗体相结合的其它抗原 ,如红细胞表面相对分子质量为 40× 10 3 的分子 ,猪胚胎脑细胞上相对分子质量为 2 10× 10 3 、10 5× 10 3 及 5 0× 10 3 的抗原分子等。结论　α Gal是异种移植超急性排斥反应的主要靶抗原 ,除α Gal外还存在有待进一步研究的非α Gal。     

异种移植的研究进展

供体器官和细胞的匮乏限制了临床同种移植的发展.开展以猪为供体的异种移植研究是缓解供体短缺的重要方法.目前,猪的胰岛细胞、神经元细胞、肝细胞和角膜移植已初步应用于临床,但实体器官移植,如心脏、肝脏、肾脏等仍存在较大的免疫障碍和生理屏障,距离临床应用尚有不小的差距.随着表达一种或多种人的免疫和凝血调节基因猪的出现,异种移植研究取得显著进展,受体和移植器官的存活时间明显延长,而种间交叉感染的风险也较低,但免疫排斥和生理屏障仍是阻碍异种移植进入临床应用的最大障碍.本文就当前异种移植临床前研究的最新进展作一综述,希望能为相关研究者提供一些参考.     

不同方法保存的猪软骨行异种移植的实验研究

为了探索不同保存方法对猪肩胛软骨异种移植的影响,采用四种不同方法保存猪肩胛软骨,并按不同保存方法及保存时间分７组移植到日本大耳白兔背部皮下,每组５只动物,共３５只进行观察比较。①γ－射线辐射处理,４℃保存３个月为Ａ组,１个月为Ｂ组;②０．５％戊二醛磷酸缓冲液浸泡,４℃保存３个月为Ｃ组,１个月为Ｄ组;③深低温－８０℃保存３个月为Ｅ组,１个月为Ｆ组;④新鲜软骨为Ｇ组。移植术后每周一次活体检查软骨位置及大小。术后１周、１个月、３个月、６个月,每只动物取一块软骨行大体标本和光学显微镜观察,术后６个月取软骨标本行电子显微镜观察。实验结果显示：０．５％戊二醛浸泡、γ－射线辐射处理可降低软骨抗原性,４℃条件下保存以≤１个月为最佳时限,按软骨被吸收率大小,依次为Ｅ、Ｆ、Ａ、Ｂ、Ｇ、Ｃ、Ｄ组。结论：①猪肩胛软骨可作为异种移植代用材料的最佳供体之一;②猪肩胛软骨异种移植到家兔皮下,可存留达６个月;③本实验四种猪软骨保存方法,按异种移植后软骨抗原性降低和被吸收、变形程度轻重等情况相比较,以０．５％戊二醛浸泡保存方法最佳,γ－射线辐射处理次之;④０．５％戊二醛磷酸缓冲液４℃１个月是保存猪肩胛软骨供异种移植的最佳条件。     

Transmission of malaria tertiana by multi-organ donation

In this report, transmission of malaria via a liver, a kidney, and possibly a heart allograft from a single donor is described. The donor had immigrated from Cameroon to Germany 18 months before, but had no clinical signs of active malaria infection. The liver transplant recipient and one of the two kidney transplant patients developed febrile illness with the appearance of Plasmodium vivax in blood smears 5 and 6 wk after transplantation, respectively. In the heart transplant recipient, a subclinical malaria infection was suspected based on a rise of malaria antibodies late after transplantation, whereas the recipient of the second kidney allograft had no clinical or laboratory evidence of malaria. Both liver and kidney recipients with active malaria responded to medical treatment. However, the liver transplant patient developed progressive cholestasis and died 5 months after transplantation from liver failure possibly due to side effects of the malaria medication. Other cases of malaria in solid organ recipients are briefly reviewed.     

Therapeutic regulation of systemic inflammation in xenograft recipients

Inflammation is known to preclude tolerance after transplantation. We have previously shown that systemic inflammation in xenograft recipients (SIXR) precedes activation of coagulation in the absence of T cell responses. Accordingly, SIXR may amplify innate and adaptive immune responses against xenografts after pig‐to‐primate xenotransplantation, even with efficient immunosuppressive therapy. We evaluated the impact of anti‐inflammatory agents on pro‐inflammatory cytokines and chemokines in pig artery patch and heart xenograft recipients. Baboons received an artery patch (Group1, n=8) or heart (Group2, n=4) from genetically engineered pigs. All baboons received lymphodepletion with thymoglobulin (ATG) and costimulation blockade‐based immunosuppression (anti‐CD40 and/or CTLA4Ig). In Group1, baboons received either (i) no anti‐inflammatory agents (n=2), (ii) cobra venom factor (CVF, n=2), (iii) α1‐antitrypsin (AAT, n=2), or (iv) interleukin (IL)‐6 receptor antagonist (IL‐6RA, n=2). In Group2, all baboon received corticosteroids, either without (n=2) or with (n=2) IL‐6RA. Serum IFN‐γ, TNF‐α, IL‐1β, IL‐17, IL‐6, IL‐8, MCP‐1, and sCD40L levels were measured by Luminex. Fibrinogen, D‐dimers, and C‐reactive protein (C‐RP) were also measured. Recipient baboon T cell proliferation was evaluated by mixed lymphocyte reaction (MLR) before and after transplantation. Pig and baboon tissue factor (TF) mRNA levels in heart xenografts were measured by RT‐PCR. In no recipient was a marked increase in T cell response to pig cells observed after transplantation. In Groups 1 and 2, post‐transplantation levels of IFN‐γ, TNF‐α, IL‐1β, and IL‐17 remained comparable to or lower than pre‐transplant levels, except in one heart recipient that succumbed to CMV infection. In Group1, when no anti‐inflammatory agent was administered, post‐transplant levels of IL‐6, IL‐8, and MCP‐1 were elevated. After CVF, IL‐6, IL‐8, and MCP‐1 remained low. After IL‐6RA, IL‐6 and MCP‐1 were elevated. After AAT, IL‐8 was elevated. sCD40L became elevated intermittently in most recipients irrespective of the administered anti‐inflammatory agent. In Group2, IL‐6 was transiently elevated, particularly after IL‐6RA administration. MCP‐1 gradually increased by 2 months in Group2 recipients. sCD40L generally remained low except in one recipient. In Group1 and Group2 recipients, C‐RP levels were elevated except after IL‐6RA administration, while D‐dimers were elevated regardless of administration of anti‐inflammatory agent. In Group2, pig TF mRNA levels were increased in heart xenografts compared to naive pig hearts, irrespective of IL‐6 receptor antagonist administration. Additionally, baboon TF mRNA levels were detectable in heart xenografts, but not in naive pig hearts. Some pro‐inflammatory cytokines and chemokines are elevated in xenograft recipients, even with efficient T cell‐directed immunosuppressive therapy. Persistent elevation of D‐dimers, and individual cytokines and chemokines suggest a continuous inflammatory response, despite administration of anti‐inflammatory agents. Systemic administration of combined anti‐inflammatory agents as well as complement regulation may be essential to prevent SIXR after xenotransplantation.     

Human Herpesvirus 8 (HHV8) Transmission and Related Morbidity in Organ Recipients

The aims of the study were to assess the risk of HHV8 transmission resulting from organ transplantation, and related morbidity in liver, heart and kidney transplant recipients. Donor and recipient serologies were screened between January 1, 2004 and January 1, 2005 using HHV8 indirect immunofluorescence latent assay (latent IFA) and indirect immunofluorescent lytic assay (lytic IFA). Recipients negative for latent IFA with a donor positive for at least one test were sequentially monitored for HHV8 viremia and underwent serological tests over a period of 2 years. The results showed that among 2354 donors, HHV8 seroprevalence was 9.9% (lytic IFA) and 4.4% (latent IFA). A total of 454 organ recipients (281 renal, 116 liver and 57 heart) were monitored over a 2‐year period. Seroconversion was observed in 12 patients (cumulative incidence 28%) whose donor had positive latent IFA and in 36 patients (cumulative incidence 29%) whose donors were positive only for lytic IFA, without differences across types of transplants. Positive HHV8 viremia was detected in only 4 out of 89 liver transplant recipients during follow‐up and not in recipients of other types of transplant. Two liver transplant recipients and one kidney transplant recipient developed KS. In conclusion, although HHV8 transmission is a frequent event after organ transplantation, HHV8‐related morbidity is rather rare but can be life threatening. Donor screening is advisable for monitoring HHV8 seronegative liver transplant recipients.     

猪到猕猴异种心脏异位移植术的手术配合

目的：介绍猪到猕猴异位心脏移植的手术配合方法。方法：选用猪到猕猴为移植模型，配合完成异位心脏移植术21例。结果：异种移植手术受体猕猴平均存活11d，手术成功率70％。结论：要确保猕猴异种移植手术成功，除了常规方法外，充分的术前准备、术中配合是异种移植手术成功的重要环节。     

Analysis of potential porcine endogenous retrovirus (PERV) transmission in a whole-organ xenotransplantation model without interfering microchimerism

The question whether porcine xenografts can lead to porcine endogenous retrovirus (PERV) infection of recipients is critical for the evaluation of the safety of pig-to-man xenotransplantation. Unfortunately, polymerase chain reaction (PCR)-based analysis of potential PERV infections in nonhuman-primate whole-organ xenotransplantation models is hampered by false positive results due to chimeric porcine cells. To avoid the inherent analytical problem of xenomicrochimerism, we developed a non-life-supporting pig-to-primate kidney xenotransplantation model: porcine kidneys were transplanted, whereas the functioning recipient kidneys remained in situ. Subsequent to rejection (after 2 hours to 15 days), xenografts were removed, and recipients remained alive for up to 287 days. Immunosuppressive therapy based on cyclophosphamide, cyclosporine, and steroids was maintained for 28 days after transplantation. Using appropriate PCR assays, xenochimerism was found in tissue samples and partly even in peripheral blood leukocytes (PBLs) while the porcine kidneys were in situ. After graft removal, xenochimerism was no longer detectable, thus allowing analysis for possible PERV transmission.     

C1 inhibitor for prophylaxis of xenograft rejection after pig to cynomolgus monkey kidney transplantation

BACKGROUND: Early rejection of discordant porcine xenografts in primate recipients is initiated by the intragraft binding of either preformed (hyperacute xenograft rejection) or induced (acute vascular rejection) antiporcine recipient antibodies with subsequent complement activation via the classical pathway. We have investigated the efficacy of the supplemental administration of C1-inhibitor (C1-INH), a specific inhibitor of the classical complement activation pathway, for prophylaxis of xenograft rejection in a pig to primate kidney xenotransplantation setting. METHODS: Based on the results of pharmacokinetic studies performed in two nontransplanted monkeys, supplemental C1-INH therapy was administered daily to three Cynomolgus monkeys receiving a life-supporting porcine kidney transplant together with cyclophosphamide-induction/cyclosporine A/mycophenolat-mofetil/steroid immunosuppressive therapy. RESULTS: In the three monkeys receiving porcine kidney xenografts and continuous C1-INH treatment none of the grafts underwent hyperacute rejection; all xenografts showed initial function. Recipient survival was 13, 15, and 5 days. No graft was lost due to acute vascular rejection. All animals died with a functioning graft (latest creatinine 96, 112, and 96 micromol/liter) due to bacterial septicemia. CONCLUSION: We conclude that, in our model, supplemental C1-INH therapy together with a standard immunosuppressive regimen can be helpful for prevention of xenograft rejection in a pig to primate kidney xenotransplantation setting. The optimal dose and duration of C1-INH treatment, however, has yet to be determined.     

Up to 9-day survival and control of thrombocytopenia following alpha1,3-galactosyl transferase knockout swine liver xenotransplantation in baboons

Kim K, Schuetz C, Elias N, Veillette GR, Wamala I, Varma M, Smith RN, Robson SC, Cosimi AB, Sachs DH, Hertl M. Up to 9‐day survival and control of thrombocytopenia following GalT‐KO swine liver xenotransplantation in baboons. Xenotransplantation 2012; 19: 256–264.. © 2012 John Wiley & Sons A/S. Abstract: Background:  With standard miniature swine donors, survivals of only 3 days have been achieved in primate liver‐transplant recipients. The recent production of alpha1,3‐galactosyl transferase knockout (GalT‐KO) miniature swine has made it possible to evaluate xenotransplantation of pig organs in clinically relevant pig‐to‐non‐human primate models in the absence of the effects of natural anti‐Gal antibodies. We are reporting our results using GalT‐KO liver grafts. Methods:  We performed GalT‐KO liver transplants in baboons using an immunosuppressive regimen previously used by our group in xeno heart and kidney transplantation. Post‐operative liver function was assessed by laboratory function tests, coagulation parameters and histology. Results:  In two hepatectomized recipients of GalT‐KO grafts, post‐transplant liver function returned rapidly to normal. Over the first few days, the synthetic products of the donor swine graft appeared to replace those of the baboon. The first recipient survived for 6 days and showed no histopathological evidence of rejection at the time of death from uncontrolled bleeding, probably caused by transfusion‐refractory thrombocytopenia. Amicar treatment of the second and third recipients led to maintenance of platelet counts of over 40 000 per μl throughout their 9‐ and 8‐day survivals, which represents the longest reported survival of pig‐to‐primate liver transplants to date. Both of the last two animals nevertheless succumbed to bleeding and enterococcal infection, without evidence of rejection. Conclusions:  These observations suggest that thrombocytopenia after liver xenotransplantation may be overcome by Amicar therapy. The coagulopathy and sepsis that nevertheless occurred suggest that additional causes of coagulation disturbance must be addressed, along with better prevention of infection, to achieve long‐term survival.     

清除补体避免猪到猕猴异种心脏移植超急性排斥反应的实验研究

目的 观察纯化的眼镜蛇毒因子(CVF)对猪到狱猴异种心脏移植超急性排斥反应的影响。方法 以幼猪为供者，施行猪到狱猴腹腔内异位心脏移植，实验组(n＝4)使用CVF完全清除受者体内补体，对照组(n＝5)不使用CVF，两个组术后均采用环抱素A、甲泼尼龙和环磷酰胺抑制排斥反应，通过检测血清C3、C4水平及总补体活性验证CVF的效果，移植心停跳时切取移植心进行病理检查。结果 在使用CVF后，实验组血清C3降为0，总补体活性CH50值也几乎为0，末发现明显毒副反应，移植猪心存活时间平均为lld，最长达13d，病理学提示均发生了延迟性异种排斥反应；对照组3个移植心在移植后60min内发生超急性排斥反应，另2个分别存活22h及6d。结论 纯化的CVF有良好的清除补体的作用，且末见明显副作用；使用CVF可克服猪到狱猴异种心脏移植超急性排斥反应的发生。     

Pre-clinical model of composite foetal pig pancreas fragment/renal xenotransplantation to treat renal failure and diabetes

Hawthorne WJ, Simond DM, Stokes R, Patel AT, Walters S, Burgess J, O’Connell PJ. Pre‐clinical model of composite foetal pig pancreas fragment/renal xenotransplantation to treat renal failure and diabetes. Xenotransplantation 2011; 18: 390–399. © 2011 John Wiley & Sons A/S. Abstract: Background: Development of a limitless source of β cells for xenotransplantation into patients suffering type 1 diabetes and renal failure that can control their diabetes and provide normal renal function in one procedure would be a major achievement. For the islet tissue to survive transplantation, as an islet‐kidney composite graft this would have significant advantages. It would simplify the surgical procedure; remove the complications caused by the exocrine pancreas whilst reversing diabetes and uraemia. It was our hypothesis that a composite foetal porcine pancreas fragment (FPPF)/renal graft could achieve these objectives in a large pre‐clinical animal model as a means to establish whether this would be feasible before moving to the clinic. Methods: Inbred ‘Westran’ pig FPPF were transplanted under the kidney capsule of syngeneic Westran pig recipients without immunosuppression. Following maturation of the FPPF under the renal subcapsular space of this recipient, this kidney bearing the composite FPPF piggyback graft was removed and transplanted into another nephrectomized and pancreatectomized recipient to demonstrate function. Results: Under the kidney capsule of the first transplant group (n = 6), the FPPF‐transplanted tissue developed and matured to form islet cell nests. These composite FPPF/renal grafts were then successfully removed and transplanted into the second functional assessment recipient group. This second group of six composite FPPF/renal‐grafted pigs had normal renal function for more than 44 days and normal glucose homoeostasis without exogenous insulin as assessed by normal glucose tolerance tests, K values and normal glucagon secretion. Histological analysis showed despite the ischaemic insult during the composite kidney transplant procedure, there was appropriate development of islet‐like structures up to and beyond 224 days after the original transplantation under the kidney capsule. Conclusions: This study shows that the use of composite FPPF/renal grafts can cure both diabetes and renal failure with a single‐transplant procedure. Using such composite grafts for xenotransplantation would simplify the surgical procedure and protect the islet graft from the immediate innate immune response.     

Experimental multivisceral xenotransplantation

Abstract: Background: Organ shortage impairs the proposition of multivisceral transplantation to treat multiple organ failure. Interspecies (xeno) transplantation is a valid solution for organ shortage; however, suitable models of this advance are lacking. We describe an effective model of multivisceral xenotransplantation to study hyperacute rejection. Methods: Under general anesthesia, we in block recovered the distal esophagus, stomach, small bowel, colon, liver, pancreas, spleen, and kidneys from donors and implanted heterotopically in the lower abdomen of recipients. Animals were divided into four groups: I—canine donor, swine recipient (n = 6); II – swine donor, canine recipient (n = 5); III—canine donor, canine recipient (n = 4); and IV—swine donor, swine recipient (n = 5). Groups I and II comprised experimental (xenotransplantation) and III and IV control groups (allotransplantation). During the experiment, we appraised recipient evolution and graft modification by sequential biopsy up to 3 h. At this time, we killed animals for autopsy (experimental end point). Results: We accomplished all experiments successfully. Every grafts attained customary appearance and convenient urine output immediately after unclamp. Around 15 min after reperfusion, xenografts achieved signs of progressive hyperacute rejection and absence of urine output. At the end of experiments we observed moderate to severe hyperacute rejection at small bowel, colon, mesenteric lymph node, liver, spleen, pancreas, and kidney, while stomach and esophagus achieved mild lesions. In contrast, allograft achieved normal or minimum ischemia/reperfusion injury and constant urine output. Conclusion: The present procedure assembles a simple and effective model to study multivisceral xenotransplantation and may ultimately spread researches toward hyperacute rejection.