1。供体手术<ol><li>应该保持供体鼠禁食24小时（水/葡萄糖溶液的免费访问）。 </li><li> ，引起吸入异氟醚麻醉，开始以2％的标准雾化器，然后降低到1％后进行剖腹手术。执行脚趾捏了把检查镇静。 </li><li>刮腹部和清洁皮肤准备3次（Kodan）。然后执行后正中切口皮下给药的镇痛。 </li><li>后移植物包裹在生理盐水浸泡过的纱布，分离胰腺和升结肠，轻轻地用一个Q-尖端（6倍放大倍率的显微镜下的手术）的生理之间的粘连。 </li><li> 7-0丝，右和中间回盲部结肠血管结扎和分裂。之后蔓延到升结肠右侧肠系膜上静脉（SMV），可以发现回盲部，右，中结肠血管结扎和部门使用7-0关系。 </li><li>向上缩回胃，从而使整个SMV的理顺和暴露。退回时使用一只蚊子夹。钳持有的形成形状的橡皮泥质量。 </li><li>从SMV的胰十二指肠静脉结扎和分裂。 ，必须仔细确定所有小从SMV的胰十二指肠静脉，结扎用7-0丝和分之前可以从胰腺组织移植物。 </li><li>失去结缔组织包括所有SMV和腹主动脉之间的淋巴管结扎和分裂。与接枝仍然在腹部右侧，失去包括SMV和腹主动脉是可访问所有的淋巴管之间的结缔组织。这结缔组织必须使用7-0丝连接，并从移植肠分为以避免术后lymphorrhea的。 </li><li>结扎及分右肾动脉。后分为结缔组织，右肾动脉变得accessibl的e和分离结扎7-0丝。 </li><li>全身heparinise的大鼠，通过阴茎静脉使用200个单位的肝素IV。 </li><li>边缘动脉结扎，然后再除以十二指肠空肠交界处的小肠和回肠末端。 </li><li>近端主动脉连接的SMA的起源。合流与脾静脉门静脉横断。移植物与主动脉段SMA血管蒂组成的收获。 </li></ol> 2。 Backtable程序<ol><li>用3ml大学在4℃UW液（UW）通过主动脉导管灌注移植和灌溉用30毫升的泌尿Nebacetin氮营养液在4°C（流明灌溉是强制性的肠腔从空肠端） 。 </li></ol>提取移植，主动脉导管后，立即用3毫升冷UW液灌注。对于这一点，20 G静脉导管上使用10毫升注射器。应当观察到的灌流液，从分割的门静脉自由流出。对于肠道Nebacetin灌溉，50毫升注射器使用。 <ol start="2"><li>移植物存放在4℃UW液的准备过程中的收件人。 </li></ol> 3。接收方操作<ol><li>应保存的收件人大鼠禁食24小时（水/葡萄糖溶液的免费访问）。 </li><li> ，引起吸入异氟醚麻醉，开始以2％的标准雾化器，然后降低到1％后进行剖腹手术。执行脚趾捏了把检查镇静。 </li><li>刮腹部和清洁皮肤准备3次（Kodan）。然后执行卡洛芬5毫克/公斤的资深大律师术中镇痛皮下给药后正中切口。 </li><li>生理盐水浸湿的纱布包裹的收件人肠道，并把它放在收件人的胸部。 </li><li>直言Q-提示，打开后腹膜，暴露腹部信号主动脉和下腔静脉的正下方的肾血管的电平下降到髂血管，如果必要还可以使用microscissors。结扎的小腰和脊髓tribuaries的主动脉和下腔静脉用7-0丝，以避免失血。 （要做到这一点，在手术显微镜放大到16倍。） </li><li>交叉钳位低于左侧肾血管近侧和远侧使用微血管片段上方的髂骨分支的主动脉和下腔静脉。只有一个夹具近端和远端同时夹住两艘船。切开两艘船前方使用microknife，洗出剩余的血。 </li><li>创建一个到另一侧吻合移植的主动脉段和收件人的腹主动脉采用连续10-0的聚丙烯缝线之间..最初，接枝上腹部的右侧（大鼠的头部定位在12点）来执行的较低的逗留缝合动脉吻合和捆扎的后壁线圈被放置。钍烯，被翻转的接枝到左侧腹部（在9点钟位置的大鼠的头），以暴露和缝合吻合术的前壁。 </li><li>同样到另一侧吻合之间的移植门静脉和收件人的IVC进行连续缝合用10-0的聚丙烯。与大鼠仍然侧身躺着（头在9点钟的位置）中，接枝位于腹部的左侧和放置低级逗留缝合。吻合术开始与从容器内部的背面壁。低级逗留缝合后是并列的，前壁线圈可以从外部进行。 </li><li>移除的前端夹具第一，然后由上夹具。任何控制的直接压力，采用Q-提示吻合口出血。移植应平等和快速再灌注检查。 </li><li>切除整个收件人的小肠的肠系膜血管结扎后。收件人进行次全切除肠切除术，保留2-3厘米的亲ximal空肠和回肠末端1厘米。 </li><li>还原肠溶连续性由近端（空肠 - 空肠造口术）和远端（回肠回肠造口术）最终结束肠吻合用一个中断的一个层缝合用6-0 Monocryl。需要完成约16缝合吻合。 </li><li>直到清洁用生理盐水冲洗腹腔。管理2毫升生理盐水腹腔内补液。然后关闭腹部的肌肉层，加上一个连续的皮肤缝合用3-0薇乔连续缝合。 </li><li>在术后的大鼠应保持空腹（水和葡萄糖溶液），另外24小时，然后重新启动标准大鼠饲料和水自由采食。应给予镇痛卡洛芬3日（见剂量下面）。 </li></ol>

<ol>
	<li>Abu-Elmagd, K. M., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Five+Hundred+Intestinal+and+Multivisceral+Transplantations+at+a+Single+Center:+Major+Advances+With+New+Challenges.">Five Hundred Intestinal and Multivisceral Transplantations at a Single Center: Major Advances With New Challenges.</a> Ann. Surg. 250 (4), 567-56 (2009).</li><li>Berney, T., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Portal+versus+systemic+drainage+of+small+bowel+allografts:+comparative+assessment+of+survival,+function,+rejection,+and+bacterial+translocation.">Portal versus systemic drainage of small bowel allografts: comparative assessment of survival, function, rejection, and bacterial translocation.</a> J. Am. Coll. Surg. 195 (6), 804 (2002).</li><li>Fishbein, T. M. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Intestinal+transplantation.">Intestinal transplantation.</a> N. Engl. J. Med. 361 (10), 998 (2009).</li><li>Hernandez, F., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Is+portal+venous+outflow+better+than+systemic+venous+outflow+in+small+bowel+transplantation?+Experimental+study+in+syngeneic+rats.">Is portal venous outflow better than systemic venous outflow in small bowel transplantation? Experimental study in syngeneic rats.</a> J. Pediatr. Surg. 40 (2), 336 (2005).</li><li>Monchik, G. J., Russell, P. S. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Transplantation+of+small+bowel+in+the+rat:+technical+and+immunological+considerations.">Transplantation of small bowel in the rat: technical and immunological considerations.</a> Surgery. 70 (5), 693 (1971).</li><li>Murase, N., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Graft-versus-host+disease+after+brown+Norway-to-Lewis+and+Lewis-to-Brown+Norway+rat+intestinal+transplantation+under+FK506.">Graft-versus-host disease after brown Norway-to-Lewis and Lewis-to-Brown Norway rat intestinal transplantation under FK506.</a> Transplantation. 55 (1), 1 (1993).</li><li>Murase, N., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Immunomodulation+of+intestinal+transplant+with+allograft+irradiation+and+simultaneous+donor+bone+marrow+infusion.">Immunomodulation of intestinal transplant with allograft irradiation and simultaneous donor bone marrow infusion.</a> Transplant Proc. 31 (1-2), 565 (1999).</li><li>Pech, T., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Perioperative+infliximab+application+ameliorates+acute+rejection+associated+inflammation+after+intestinal+transplantation.">Perioperative infliximab application ameliorates acute rejection associated inflammation after intestinal transplantation.</a> Am. J. Transplant. 10 (11), 2431 (2010).</li><li>Schaefer, N., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Resident+macrophages+are+involved+in+intestinal+transplantation-associated+inflammation+and+motoric+dysfunction+of+the+graft+muscularis.">Resident macrophages are involved in intestinal transplantation-associated inflammation and motoric dysfunction of the graft muscularis.</a> Am J Transplant. 7 (5), 1062 (2007).</li><li>Schaefer, N., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Mechanism+and+impact+of+organ+harvesting+and+ischemia-reperfusion+injury+within+the+graft+muscularis+in+rat+small+bowel+transplantation.+Transplant.">Mechanism and impact of organ harvesting and ischemia-reperfusion injury within the graft muscularis in rat small bowel transplantation. Transplant.</a> Proc. 38 (6), 1821 (2006).</li><li>Schaefer, N., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Acute+rejection+and+the+muscularis+propria+after+intestinal+transplantation:+the+alloresponse,+inflammation,+and+smooth+muscle+function.">Acute rejection and the muscularis propria after intestinal transplantation: the alloresponse, inflammation, and smooth muscle function.</a> Transplantation. 85 (10), 1465 (2008).</li><li>Xue, L., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Surgical+experience+of+refined+3-cuff+technique+for+orthotopic+small-bowel+transplantation+in+rat:+a+report+of+270+cases.">Surgical experience of refined 3-cuff technique for orthotopic small-bowel transplantation in rat: a report of 270 cases.</a> Am. J. Surg. 198 (1), 110 (2009).</li><li>Zhang, X. Q., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Simplified+techniques+in+rat+heterotopic+small+bowel+transplantation.">Simplified techniques in rat heterotopic small bowel transplantation.</a> Transplant. Proc. 38 (6), 1840 (2006).</li><li>Zhao, Y., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=The+establishment+of+a+new+en+bloc+combined+liver-small+bowel+transplantation+model+in+rats.+Transplant.">The establishment of a new en bloc combined liver-small bowel transplantation model in rats. Transplant.</a> Proc. 39 (1), 278 (2007).</li></ol>

没有利益冲突的声明。

最近采用的模型大鼠小肠移植模型中被描述为早在1970ies 5涉及异位小肠移植使用不同的技术13。异位一般程序的优点是更容易的显微外科技术，更容易获得移植物的评估，异位小肠移植有很大的缺点，不考虑的移植小肠的收缩活动功能等方面的多重相互作用黏膜屏障功能提供了广阔的主机的共生和病原体的背景下，原位移植的特点。我们的团队已获得了大量的经验，本文描述的的?...

<table border="1"><tbody><tr><td> 的试剂的名称 </td><td> 公司 </td><td> 目录编号 </td><td> 评论（可选） </td></tr><tr><td>威斯康星大学（UW）解决方案（ViaSpan） </td><td>百时美施贵宝（Bristol-Myers公司Squibb） </td><td></td><td></td></tr><tr><td>泌尿Nebacetin氮营养液</td><td>奈科明</td><td> 6967855 </td><td></td></tr><tr><td>氨苄青霉素</td><td> Ratiopharm公司</td><td></td><td></td></tr><tr><td>卡洛芬（Rimadyl） </td><td>辉瑞公司</td><td></td><td></td></tr><tr><td>普理灵10-0 unresorbable缝合</td><td>爱惜</td><td></td><td></td></tr><tr><td> Monocryl 6-0可吸收缝线</td><td>爱惜</td><td></td><td></td></tr><tr><td>薇乔3-0可吸收缝线</td><td>爱惜</td><td></td><td></td></tr><tr><td>静脉导管G 20 1.1x33毫米</td><td>布劳恩</td><td></td><td></td></tr><tr><td>静脉导管G 22 0.9x25毫米</td><td>布劳恩</td><td></td><td></td></tr><tr><td> Kodan皮肤准备</td><td>舒美公司</td><td></td><td></td></tr><tr><td> 0.9％生理盐水输液</td><td>布劳恩</td><td></td><td></td></tr><tr><td>小弯钳</td><td> FineScienceTools </td><td> 11009-13 </td><td></td></tr><tr><td>微型镊子弯曲</td><td>蛇牌</td><td> BD 333 </td><td></td></tr><tr><td>微型镊子弯曲</td><td>蛇牌</td><td> FD281R </td><td></td></tr><tr><td>科技钳直1 </td><td> WPI </td><td> 5 </td><td></td></tr><tr><td>科技钳直2 </td><td> WPI </td><td> 2 </td><td></td></tr><tr><td>微针持有人</td><td> WPI </td> &lt;TD&gt; 14081 </td><td></td></tr><tr><td>微型剪刀</td><td> FineScienceTools </td><td> 15006-09 </td><td></td></tr><tr><td>微型手术刀</td><td> MANI </td><td>眼科刀</td><td></td></tr><tr><td>微夹</td><td>蛇牌</td><td> FB329R </td><td></td></tr></tbody></table>

orthotopic small bowel transplantation in rats

小肠移植已成为公认的短肠综合征和失败的肠外营养（不可逆肠衰竭）患者的临床治疗选择。在专门的医疗中心，提高操作和管理策略导致了优异的短期和中期患者和移植物存活率，同时提供高品质的生活1,3。不同的是较常见的其他实体器官移植（ 即心脏，肝脏）许多潜在的诱导小肠移植的移植肾功能和免疫学改变的机制尚不完全清楚6,7。发作的急性排斥反应，败血症，慢性移植物功能衰竭的主要障碍仍然较为有利的长期结果，并阻碍更广泛的就业的过程中，尽管越来越多的家庭肠外营养的患者可能受益于这样的移植。小肠包含乘客白细胞的大量的，通常被称为作为肠相关的淋巴系统（GALT）肠道接枝的高免疫原性的原因，这是一部分的一部分。许多共生和病原体在肠道中的存在和靠近解释脓毒症发作的严重程度，一旦接枝粘膜的完整性受到损害（例如，通过抑制）。为了推动该领域的肠和多器官移植产生的数据更可靠和可行的动物模型是必要的。本文结合该模型的可靠性和可行性一旦确立以标准化的方式，可以在底层的复杂的分子，细胞和功能的机制所触发的小肠移植提供了宝贵的见解。我们已经成功地使用超过5年以上的在我们的实验室8-11细化所描述的过程。朱庇特的视频格式是特别有用的，表现出复杂的多项式dure，避免最初的规划，建立原位啮齿动物​​模型研究小肠移植组的陷阱。

术后正常移植的动物迅速恢复的过程中，下加热灯约1小时。低温的术后死亡率的一个重要原因，应谨慎地避免内和术后。皮下注射2.5毫升生理盐水加2.5毫升的5％葡萄糖每8个小时，第24小时，术中的流体损失，必须更换。大鼠也应该有术后第一个24小时免费使用葡萄糖溶液（或凝胶饮食）和水区。在此期间，他们应该免费使用标准大鼠饲料和水自由采食恢复​​正常进食行为。?...

Watch this Scientific Journal Video about Orthotopic Small Bowel Transplantation in Rats at JoVE.com

Orthotopic Small Bowel Transplantation in Rats

小肠移植已成为一种公认的不可逆肠衰竭患者的治疗选择。我们作为一个可靠的工具，以解决潜在的免疫和炎症过程的复杂小肠移植大鼠原位小肠移植的实验模型。

大鼠原位小肠移植

Small  bowel transplantation has become an accepted clinical option for patients with  short gut syndrome and failure of parenteral nutrition ...

orthotopic-small-bowel-transplantation-in-rats

Research

JoVE Journal

Medicine

14.1K 次观看.  University of Bonn, Germany. 小肠移植已成为一种公认的不可逆肠衰竭患者的治疗选择。我们作为一个可靠的工具，以解决潜在的免疫和炎症过程的复杂小肠移植大鼠原位小肠移植的实验模型。

视频: Orthotopic Small Bowel Transplantation in Rats

Development of Obliterative Bronchiolitis in a Murine Model of Orthotopic Lung Transplantation

Orthotopic lung transplantation in rats was first reported by Asimacopoulos and colleagues in 1971 1. Currently, this method is well accepted and standardized not only for the study of allo-rejection but also between syngeneic strains for examining mechanisms of ischemia-reperfusion injury after lung transplantation. Although the application of the rat and other large animal model 2 contributed significantly to the elucidation of these studies, the scope of those investigations is limited by the scarcity of knockout and transgenic rats. Due to no effective therapies for obliterative bronchiolitis, the leading cause of death in lung transplant patients, there has been an intensive search for pre-clinical models that replicate obliterative bronchiolitis. The tracheal allograft model is the most widely used and may reproduce some of the histopathologic features of obliterative bronchiolitis 3. However, the lack of an intact vasculature with no connection to the recipient's conducting airways, and incomplete pathologic features of obliterative bronchiolitis limit the utility of this model 4. Unlike transplantation of other solid organs, vascularized mouse lung transplants have only recently been reported by Okazaki and colleagues for the first time in 2007 5. Applying the basic principles of the rat lung transplant, our lab initiated the obliterative bronchiolitis model using minor histoincompatible antigen murine orthotopic single-left lung transplants which allows the further study of obliterative bronchiolitis immunopathogenesis6.

Obliterative bronchiolitis is the key impediment to the long-term survival of lung transplant recipients and the lack of a robust preclinical model precludes examining obliterative bronchiolitis immunopathogenesis. Unlike other solid organ transplants, vascularized mouse lung transplantation has only recently been developed. Here we show our independently developed obliterative bronchiolitis model after murine orthotopic single-lung transplantation.

闭塞性细支气管炎在原位肺移植小鼠模型的发展

Orthotopic lung transplantation in rats was first reported by Asimacopoulos and colleagues in 1971 1. Currently, this method is well accepted and ...

科研

医学

Orthotopic Liver Transplantation in Rats

Clinical progress in the field of liver transplantation has been largely supported by animal models1,2. Since the publication of the first orthotopic rat liver transplantation in 1979 by Kamada et al.3, this model has remained the gold standard despite various proposed alternative techniques4. Nevertheless, its broader use is limited by its steep learning curve5.
In this video paper, we show a simple and easy-to-establish revision of Kamada's two-cuff technique. The suprahepatic vena cava anastomosis is performed manually with a running suture, and the vena porta and infrahepatic vena cava anastomoses are performed utilizing a quick-linker cuff system6. Manufacturing the quick-linker kit is shown in a separate video paper.

We present an easy-to-establish revision of the classical two-cuff technique for orthotopic liver transplantation in rat.

大鼠原位肝移植

Clinical progress in the field of liver transplantation has been largely supported by animal models1,2. Since the publication of the first orthotopic rat ...

Orthotopic Aortic Transplantation in Mice for the Study of Vascular Disease

Vascular procedures involving anastomoses in the mouse are generally thought to be difficult and highly dependent on the skill of the individual surgeon. This is largely true, but there are a number of important principles that can reduce the difficulty of these procedures and enhance reproducibility. Orthotopic aortic transplantation is an excellent procedure in which to learn these principles because it involves only two end-to-end anastomoses, but requires good suturing technique and handling of the vessels for consistent success. This procedure begins with the procurement of a length of abdominal aorta from a donor animal, followed by division of the native aorta in the recipient. The procured aorta is then placed between the divided ends of the recipient aorta and sutured into place using end-to-end anastomoses. To accomplish this objective successfully requires a high degree of concentration, good tools, a steady hand, and an appreciation of how easily the vasculature of a mouse can be damaged, resulting in thrombosis. Learning these important principles is what occupies most of the beginner's time when learning microsurgery in small rodents. Throughout this protocol, we refer to these important points. This model can be used to study vascular disease in a variety of different experimental systems1-8. In the context shown here, it is most often used for the study of post-transplant vascular disease, a common long-term complication of solid organ transplantation in which intimal hyperplasia occurs within the allograft. The primary advantage of the model is that it facilitates quantitative morphometric analyses and the transplanted vessel lies contiguous to the endogenous vessel, which can serve as an additional control9. The technique shown here is most often used for mice weighing 18-25 grams. We have accumulated most of our experience using the C57BL/6J, BALB/cJ, and C3H/HeJ strains.

We describe a technique in which a section of the abdominal aorta from a mouse is transplanted orthotopically to just below the renal arteries in an allogeneic or syngeneic recipient. This technique can be useful in studies in which transplantation of large arteries of uniform size is deemed advantageous.

原位主动脉瓣移植在小鼠血管疾病的研究

Vascular procedures involving anastomoses in the mouse are generally thought to be difficult and highly dependent on the skill of the individual surgeon. ...

Orthotopic Hind Limb Transplantation in the Mouse

In vivo animal model systems, and in particular mouse models, have evolved into powerful and versatile scientific tools indispensable to basic and translational research in the field of transplantation medicine. A vast array of reagents is available exclusively in this setting, including mono- and polyclonal antibodies for both diagnostic and interventional applications. In addition, a vast number of genotyped, inbred, transgenic, and knock out strains allow detailed investigation of the individual contributions of humoral and cellular components to the complex interplay of an immune response and make the mouse the gold standard for immunological research. 
Vascularized Composite Allotransplantation (VCA) delineates a novel field of transplantation using allografts to replace "like with like" in patients suffering traumatic or congenital tissue loss. This surgical methodological protocol shows the use of a non-suture cuff technique for super-microvascular anastomosis in an orthotopic mouse hind limb transplantation model. The model specifically allows for comparison between established paradigms in solid organ transplantation with a novel form of transplants consisting of various different tissue components. Uniquely, this model allows for the transplantation of a viable vascularized bone marrow compartment and niche that have the potential to exert a beneficial effect on the balance of immune acceptance and rejection. This technique provides a tool to investigate alloantigen recognition and allograft rejection and acceptance, as well as enables the pursuit of functional nerve regeneration studies to further advance this novel field of transplantation.

This novel model for orthotopic hind limb transplantation in the mouse, applying a non-suture cuff technique for super-microvascular anastomosis, provides a powerful tool for in&#160;vivo mechanistic immunological research related to vascularized composite allotransplantation (VCA).

原位后肢移植中的鼠标

In vivo animal model systems, and in particular mouse models, have evolved into powerful and versatile scientific tools indispensable to basic and ...

Transarterial Administration of Oncolytic Viruses for Locoregional Therapy of Orthotopic HCC in Rats

Hepatocellular carcinoma (HCC) is a disease with limited treatment options and poor prognosis. In recent years, oncolytic virotherapies have proven themselves to be potentially powerful tools to fight malignancy. Due to the unique dual blood supply in the liver, it is possible to apply therapies locally to orthotopic liver tumors, which are predominantly fed by arterial blood flow. We have previously demonstrated that hepatic arterial delivery of oncolytic viruses results in safe and efficient transduction efficiency of multifocal HCC lesions, resulting in significant prolongation of survival in immune competent rats. This procedure closely mimics the application of transarterial embolization in patients, which is the standard palliative care provided to many HCC patients. The ability to administer tumor therapies through the hepatic artery in rats allows for a highly sophisticated preclinical model for evaluating novel viral vectors under development. Here we describe the detailed protocol for microdissection of the hepatic artery for infusion of oncolytic virus vectors to treat orthotopic HCC.

Oncolytic virotherapies are under development as novel therapeutics for the treatment of hepatocellular carcinoma (HCC). Here we describe a method for locoregional therapy of HCC via hepatic arterial administration of oncolytic virus.

溶瘤病毒的Transarterial管理局大鼠原位肝癌的局部治疗

Hepatocellular carcinoma (HCC) is a disease with limited treatment options and poor prognosis.  In recent years, oncolytic virotherapies have proven ...

A Pre-Clinical Porcine Model of Orthotopic Heart Transplantation

Fifty-years following the first successful report, cardiac transplantation remains the gold-standard treatment for eligible patients with advanced heart failure. Multiple small-animal models of heart transplantation have been used to study the acute and long-term effects of novel therapies. However, few are tested and demonstrated success in clinical trials. It is of critical importance to evaluate new therapies in a clinically relevant large-animal model for efficient and reliable translation of basic studies&#39;&#160;findings. Here, we describe a pre-clinical large-animal (porcine) model of orthotopic heart transplantation that has been firmly established and previously used to investigate novel cardioprotective strategies. This procedure focuses on acute ischemia-reperfusion injury and is a reliable method to investigate novel interventions which have been tested and validated in smaller experimental models, such as the murine model. We demonstrate its usefulness in assessing cardiac performance during the early post-transplantation period and other potential possibilities enabled by the model.

Here, we describe a pre-clinical large-animal (porcine) model of orthotopic heart transplantation that has been firmly established and utilized to investigate novel cardioprotective strategies.

正交心脏移植的临床前猪模型

Fifty-years following the first successful report, cardiac transplantation remains the gold-standard treatment for eligible patients with advanced heart ...

Orthotopic Rat Kidney Transplantation: A Novel and Simplified Surgical Approach

Kidney transplantation offers increased survival rates and improved quality of life for patients with end-stage renal disease, as compared to any type of renal replacement therapy. Over the past few decades, the rat kidney transplantation model has been used to study the immunological phenomena of rejection and tolerance. This model has become an indispensable tool to test new immunomodulatory pharmaceuticals and regimens prior to proceeding with expensive preclinical large animal studies.
This protocol provides a detailed overview of how to reliably perform orthotopic kidney transplantation in rats. This protocol includes three distinctive steps that increase the probability of success: perfusion of the donor kidney by flushing through the portal vein and the use of a cuff system to anastomose the renal veins and ureters, thereby decreasing cold and warm ischemia times. Using this technique, we have achieved survival rates beyond 6 months with normal serum creatinine in animals with syngeneic or tolerant kidney transplants. Depending on the aim of the study, this model can be modified by pre- or posttransplant treatments to study the acute, chronic, cellular, or antibody-mediated rejection. It is a reproducible, reliable, and cost-effective animal model to study different aspects of kidney transplantation.

The purpose of this manuscript and protocol is to explain and demonstrate in detail the surgical procedure of orthotopic kidney transplantation in rats. This method is simplified to achieve the correct perfusion of the donor kidney and shorten the reperfusion time by using the venous and ureteral cuff anastomosis technique.

大鼠原位肾移植: 一种新的简化的手术方法

Kidney transplantation offers increased survival rates and improved quality of life for patients with end-stage renal disease, as compared to any type of ...

Reduced Complications after Arterial Reconnection in a Rat Model of Orthotopic Liver Transplantation

The rat orthotopic liver transplantation (OLT) model is a powerful tool to study acute and chronic rejection. However, it is not a complete representation of human liver transplantation due to the absence of arterial reconnection. Described here is a modified transplantation procedure that includes the incorporation of hepatic artery (HA) reconnection, leading to a marked improvement in transplant outcomes. With a mean anhepatic time of 12 min and 14 s, HA reconnection results in improved perfusion of the transplanted liver and an increase in long-term recipient survival from 37.5% to 88.2%. This protocol includes the use of 3D-printed cuffs and holders to connect the portal vein and infrahepatic inferior vena cava. It can be implemented for studying multiple aspects of liver transplantation, from immune response and infection to technical aspects of the procedure. By incorporating a simple and practical method for arterial reconnection using a microvascular technique, this modified rat OLT protocol closely mimics aspects of human liver transplantation and will serve as a valuable and clinically relevant research model.

The goal of this study is to modify the rat orthotopic liver transplant model to better represent human liver transplantation and improve recipient survival. The presented method reestablishes hepatic arterial inflow by connecting the donor liver&#39;s common hepatic artery to the recipient liver&#39;s proper hepatic artery.

矫形肝移植大鼠模型中动脉重联后并发症减少

The rat orthotopic liver transplantation (OLT) model is a powerful tool to study acute and chronic rejection. However, it is not a complete representation ...

Orthotopic Kidney Auto-Transplantation in a Porcine Model Using 24 Hours Organ Preservation And Continuous Telemetry

In the present era of organ transplantation with critical organ shortage, various strategies are employed to expand the pool of available allografts for kidney transplantation (KT). Even though, the use of allografts from extended criteria donors (ECD) could partially ease the shortage of organ donors, ECD organs carry a potentially higher risk for inferior outcomes and postoperative complications. Dynamic organ preservation techniques, modulation of ischemia-reperfusion and preservation injury, and allograft therapies are in the spotlight of scientific interest in an effort to improve allograft utilization and patient outcomes in KT.
Preclinical animal experiments are playing an essential role in translational research, especially in the medical device and drug development. The major advantage of the porcine orthotopic auto-transplantation model over ex vivo or small animal studies lies within the surgical-anatomical and physiological similarities to the clinical setting. This allows the investigation of new therapeutic methods and techniques and ensures a facilitated clinical translation of the findings. This protocol provides a comprehensive and problem-oriented description of the porcine orthotopic kidney auto-transplantation model, using a preservation time of 24 hours and telemetry monitoring. The combination of sophisticated surgical techniques with highly standardized and state-of-the-art methods of anesthesia, animal housing, perioperative follow up, and monitoring ensure the reproducibility and success of this model.

Large animal models play an essential role in preclinical transplantation research. Due to its similarities to the clinical setup, the porcine model of orthotopic kidney auto-transplantation described in this article provides an excellent in vivo setting for the testing of organ preservation techniques and therapeutic interventions.

使用24小时器官保存和连续遥测的猪模型中正交肾自动移植

In the present era of organ transplantation with critical organ shortage, various strategies are employed to expand the pool of available allografts for ...

Left Lung Orthotopic Transplantation in a Juvenile Porcine Model for ESLP

Lung transplantation is the gold-standard treatment for end-stage lung disease, with over 4,600 lung transplantations performed worldwide annually. However, lung transplantation is limited by a shortage of available donor organs. As such, there is high waitlist mortality. Ex situ lung perfusion (ESLP) has increased donor lung utilization rates in some centers by 15%-20%. ESLP has been applied as a method to assess and recondition marginal donor lungs and has demonstrated acceptable short- and long-term outcomes following transplantation of extended criteria donor (ECD) lungs. Large animal (in vivo) transplantation models are required to validate ongoing in vitro research findings. Anatomic and physiologic differences between humans and pigs pose significant technical and anesthetic challenges. An easily reproducible transplant model would permit the&#160;in vivo&#160;validation of current ESLP strategies and the preclinical evaluation of various interventions designed to improve donor lung function. This protocol describes a porcine model of orthotopic left lung allotransplantation. This includes anesthetic and surgical techniques, a customized surgical checklist, troubleshooting, modifications, and the benefits and limitations of the approach.

This protocol describes a juvenile porcine model of orthotopic left lung allotransplantation designed for use with ESLP research. Focus is made on anesthetic and surgical techniques, as well as critical steps and troubleshooting.

ESLP幼猪模型中的左肺原位移植

Lung transplantation is the gold-standard treatment for end-stage lung disease, with over 4,600 lung transplantations performed worldwide annually. ...