资金来源：本工作由国家卫生补助HL067177，HL096845研究院支持，P01AI084853向社会福利署署长

1。捐助者的程序<ol><li>利用无菌技术进行所有的外科手术。没有抗生素给捐赠者和接受者小鼠。 </li><li>对诱导捐助老鼠麻醉开始用5％的异氟醚。 </li><li>鼠标orotracheally插管用20号静脉导管，然后放在啮齿动物呼吸机，使用125次/分钟，约0.5毫升的潮气量（其体重的2％）的速度在100％的氧气。 </li><li>吸入1-2％的异氟醚维持麻醉。 </li><li>捐助鼠标放置在仰卧位，用70％酒精prepped。 </li><li> laparosternotomy进行联合中线和横切口。 </li><li>肝素100 U /公斤注入下腔静脉（IVC），略低于肝脏。 </li><li>隔膜被切断沿肋骨向脊柱腹侧附件，胸腔被切割的胸部两侧暴露墙上的脖子。 </li><li>切开膈肌水平下腔静脉后，右心耳切肺部冲洗2的冷却毫升（4°ç）乳酸林格氏液的注射液和0.1肝素毫升通过1，肺动脉根（横切口PA）的躯干。 </li><li>逮捕三分之二呼气末通胀通风，心脏，肺块切除冰（4℃）保存。 </li><li>捐助左肺准备的收件人由袖口附件。肺韧带，切开肺静脉（PV）。肺门取出食道和主动脉。 </li><li>确定的PA，位于肺门最颅方面，以及附加的（Br）的主支气管。仔细解剖支气管的PA。 </li><li> PA的袖口是由24号静脉注射（IV）导管，并下调至0.5毫米，0.7毫米的延伸长度。 </li><li>袖口的整个表面，然后打磨，以方便anastoMOSIS。 </li><li>支气管袖来自20号静脉导管，并削减1.0毫米，0.7毫米的延伸长度。 </li><li>使用相同的材​​料，光伏袖口不同与捐助鼠标的重量。具体来说，对小鼠24-27克的袖口大小是22号，在0.7毫米延伸长度0.7毫米。对于重27-32克的小鼠，研究利用20号导管，在0.7毫米延伸长度为0.7毫米。 </li><li>袖口的PA，PV和Br的末端插入，并用9-0缝线担保。 </li><li>供肺被刷新和入库前的无菌肝素的无菌生理盐水冲洗。供肺，然后在无菌生理盐水中浸泡消毒纱布上冰（4℃），这使肺很干净，无菌包装。 </li><li>一个微血管钳放在支气管进入气道，防止乳酸林格氏项。 </li></ol> 2。收件人程序<ol><li>诱导的anesthesia和机械通风是相同的，为上述捐助。 </li><li>左侧胸壁被剃光，用70％酒精和外科领域搭着prepped。 </li><li>在左侧第三肋间开胸手术切口，延长切口，背部脊柱，和微血管钳置于毗邻心脏左侧肺血管和支气管。你可以看到在脑神经方面的PA，光伏在他们之间的尾端肺门和Br。 </li><li>使用柔和的止血牵引，导致PA，Br和光伏轻度紧张，左肺被拉到胸腔，而离开中央肺门结构夹住。 </li><li>钝性分离放置9-0缝合的位置，周围的PA，PV和Br松散分离的PA，PV和Br。 </li><li>是完全从它的外膜鞘，小横切口约一船的周长的四分之一解剖后的PA制成的前壁，留下完整的背动脉的延续。 </li><li>冷，乳酸林格氏液浸泡过的纱布包裹，并准备如上所述，供体肺，然后定位到胸腔，袖口插入收件人PA，PV和Br和固定9-0缝合。 </li><li>肺门交叉钳被删除，允许再灌注损伤和通风。 </li><li>开胸切口定位到收件人胸部的肺移植后，使用5-0缝合关闭。 </li><li>鼠标被允许从麻醉中恢复。丁丙诺啡（0.05-0.15毫克/千克）管理后，立即手术，手术后2-3天，每8小时。 </li></ol> 3。代表结果我们的经验告诉我们，它需要几个月的反复实践，成为精通在小鼠肺移植模型。能力达到后，我们一chieved发生手术后七天内与死亡的96％（96/100连续手术）的围手术期存活率。两人死亡是由于出血，开始手术，，并pneumothraces其他两只老鼠的死亡原因。所有程序，热缺血时间为14.32±3.14分钟，冷缺血时间为58.51±18.06分钟。三原位肺移植组进行了研究：同系C57BL / 6→的C57BL / 6，移植：C57BL/10→的C57BL / 6和C57BL / 6→C​​57BL/10。我们只用雄性小鼠，但我们的技术还可以应用到雌性小鼠，这是因为没有显着两性之间的解剖差异。 排斥反应的病理分级进行了一项双盲临床肺移植7（ 见表1）利用标准的时尚。而我们观察到轻度或无排斥反应，在同系（C57BL / 6→的C57BL / 6），同时移植的组合开发COMPArable急性或慢性排斥反应（ 图1）。相比之下，OB明显更频繁的C57BL/10→C57BL / 6比C57BL / 6→C57BL/10组day28（ 见表1）。 <table border="1"><tbody><tr><td></td><td>只C57BL / 6→ C57BL / 6小鼠</td><td> C57BL/10→ C57BL / 6小鼠</td><td>只C57BL / 6→ C57BL/10 </td><td> P-值</td></tr><tr><td>排斥反应的病理 “A”的成绩在28天</td><td> 0.67±0.89 </td><td> * 3.33±0.82 </td><td> * 3.29±0.76 </td><td> * P &lt;0.05 </td></tr><tr><td>在21和28天的OB /共有小鼠</td><td> 0/24（0％） </td><td> ** 14/34（42.1％） </td><td> ** 2/16（12.5％） </td><td> **示P &lt;0.05 </td></tr></tbody></table> 表1。闭塞性细支气管炎移植后急性排斥反应和患病的组织学评分。急性排斥反应的评分标准CRI（“A”的成绩）teria中所述的有代表性的成果。数据代表“A”的成绩在28天移植后的平均值±标准差。数据代表各组小鼠，发达国家在21天及28移植后的OB的数量和比例。 <img alt="图1" src="/files/ftp_upload/3947/3947fig1.jpg" /> 图1。宏观结果与组织病理学肺移植后28天。 1A小组代表的宏观结果，H＆E染色的同系移植肺和右天真肺。代表小组1B和1C，H＆E和Masson染色染色BL/10肺移植，移植到收件人，分别开发的OB OB和非基本法/ 6小鼠。在1B的白色箭头标识的OB病变。 1D面板显示“基本法”/ 6肺移植移植到BL/10鼠标收件人。 在手术过程中的主要故障排除如下。 <ol><li>血流障碍：冲洗供肺​​，直到颜色变成白色。使用压力过大，可能引起肺水肿。但不推太多，以防止移植后的水肿。 </li><li>袖口插入到捐助的困难：确定有足够的长度和所附的脂​​肪和结缔组织，血管。 </li><li>吻合口出血：用Q提示申请约5分钟，受影响网站的压力。 </li><li>收件人的PA血流梗阻：主要由扭转引起的在袖口插入。如果空气在PA的观察，然后重新做吻合术是必要的。 </li><li>困难光伏吻合：光伏膜非常薄，容易流泪。选择合适的袖带大小和笔直插入收件人的PV非常轻柔。 </li><li>收件人光伏血流受阻：确保袖带的位置和方向。释放压缩支气管袖。 </li><li>气胸：这可能会造成无论是支气管穿孔由于以manipulatio，n的气道，或由于肺表面与移植过程相关的创伤穿孔。前者被视为外科手术的气道壁内孔和后者则通过oversewing肺表面用10-0尼龙缝线泄漏的处理。 </li></ol>

<ol>
	<li>Asimacopoulos, P. J., Molokhia, F. A., Pegg, C. A., Norman, J. C. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Lung+transplantation+in+the+rat.">Lung transplantation in the rat.</a> Transplant Proc. 3, 583-585 (1971).</li><li>Yoshida, S. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Surgical+technique+of+experimental+lung+transplantation+in+rabbits.">Surgical technique of experimental lung transplantation in rabbits.</a> Ann. Thorac. Cardiovasc. Surg. 11, 7-11 (2005).</li><li>McDyer, J. F. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Human+and+murine+obliterative+bronchiolitis+in+transplant.">Human and murine obliterative bronchiolitis in transplant.</a> Proc. Am. Thorac. Soc. 4, 37-43 (2007).</li><li>Sato, M., Keshavjee, S., Liu, M. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Translational+research:+animal+models+of+obliterative+bronchiolitis+after+lung+transplantation.">Translational research: animal models of obliterative bronchiolitis after lung transplantation.</a> Am. J. Transplant. 9, 1981-1987 (2009).</li><li>Okazaki, M. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=A+mouse+model+of+orthotopic+vascularized+aerated+lung+transplantation.">A mouse model of orthotopic vascularized aerated lung transplantation.</a> Am. J. Transplant. 7, 1672-1679 (2007).</li><li>Fan, L. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Neutralizing+IL-17+Prevents+Obliterative+Bronchiolitis+in+Murine+Orthotopic+Lung+Transplantation.">Neutralizing IL-17 Prevents Obliterative Bronchiolitis in Murine Orthotopic Lung Transplantation.</a> Am. J. Transplant. 11, 911-922 (2011).</li><li>Stewart, S. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Revision+of+the+1996+working+formulation+for+the+standardization+of+nomenclature+in+the+diagnosis+of+lung+rejection.">Revision of the 1996 working formulation for the standardization of nomenclature in the diagnosis of lung rejection.</a> J. Heart Lung Transplant. 26, 1229-1242 (2007).</li><li>Mizuta, T., Kawaguchi, A., Nakahara, K., Kawashima, Y. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Simplified+rat+lung+transplantation+using+a+cuff+technique.">Simplified rat lung transplantation using a cuff technique.</a> J. Thorac. Cardiovasc. Surg. 97, 578-581 (1989).</li><li>Jungraithmayr, W. M., Korom, S., Hillinger, S., Weder, W. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=A+mouse+model+of+orthotopic,+single-lung+transplantation.">A mouse model of orthotopic, single-lung transplantation.</a> J. Thorac. Cardiovasc. Surg. 137, 486-491 (2009).</li><li>Li, W. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Orthotopic+vascularized+right+lung+transplantation+in+the+mouse.">Orthotopic vascularized right lung transplantation in the mouse.</a> J. Thorac. Cardiovasc. Surg. , (2010).</li></ol>

没有利益冲突的声明。

在小鼠原位肺移植是具有挑战性的，由于显微组织的要求和极端脆弱性。袖口技术引进已允许8在大鼠原位肺移植的广泛使用。这成为在我们的实验室小鼠原位肺移植模型的发展奠定了基础。与人类不同，在小鼠和大鼠，左肺只包含一个肺叶，只有25％的肺总质量。这使得左单肺移植小鼠模型是可行的，没有循环支持系统的必要性。 我们初步的手术透露，通风和灌注肺移植是高度依赖对光伏吻合的大小。具体光伏吻合袖口大小，利用匹配的捐助者和受助人报告9。不适当的袖口上浆导致肺不张或肺移植或裂开光伏anastomosis。冈崎等人报告使用合并血管结扎和夹闭支气管5。在目前的研究中，我们使用所有肺门结构的动脉瘤夹，我们建议可缩短热缺血时间。原位左肺移植小鼠模型中的一个限制是，收件人的动物可以生存后，其移植5介导的免疫性坏死。因此，生存的研究是不可行的移植评估取决于病理检查肺移植10。 使用这种技术，我们已经制定了临床前的闭塞性细支气管炎模型小鼠。具体来说，的捐助鼠标C57BL/10和收件人的C57BL / 6。这表明对未成年人的作用，而不是主要组织相容性抗原闭塞性细支气管炎发病6。此外，我们已报道中IL-17在小鼠模型防止闭塞性细支气管炎。此模式L代表的检查和肺移植的临床肺移植手术的进步，新的研究工具。

<table border="1"><tbody><tr><td> 设备名称 </td><td> 公司 </td><td> 目录 数 </td></tr><tr><td>蔡司OPMI 6SFC-1880 </td><td>普雷斯科特公司</td><td> PMZ014 </td></tr><tr><td>哈佛鼠类呼吸的</td><td>哈佛仪器</td><td> 55-7058 </td></tr><tr><td> 20号静脉导管</td><td>泰尔茂医疗公司</td><td> 100510D </td></tr><tr><td> 22号静脉导管</td><td>泰尔茂医疗公司</td><td> 081015S </td></tr><tr><td> 24压力表静脉导管</td><td>泰尔茂医疗公司</td><td> 100522A </td></tr><tr><td> 9/0冰毒蓝维珍丝绸</td><td> ashaway线和绳索制造配套有限公司</td><td> MBVS-90 </td></tr><tr><td> 10-0爱尔康手术缝合</td><td>爱尔康公司</td><td> 8065-192101 </td></tr><tr><td> “基本法”ACK编织丝绸5-0/18inches </td><td>亨利施恩</td><td> M652630 </td></tr><tr><td>肝素钠1000单位/毫升</td><td> APP的制药</td><td> 407156 </td></tr><tr><td>优碘溶液</td><td>普渡产品</td><td> 67618-150 </td></tr><tr><td>乳酸林格氏注射液</td><td> Hospira公司</td><td> NDC 0409-7953-03 </td></tr></tbody></table><table border="1"><tbody><tr><td> 老鼠的应变 </td><td> 供应商 </td><td> 年龄，体重 </td><td> 性别，评论 </td></tr><tr><td> C57BL/10 </td><td>哈伦只Sprague-Dawley </td><td> 8-12周，25-30G </td><td>男，捐助</td></tr><tr><td> C57BL / 6小鼠</td><td>哈伦只Sprague-Dawley </td><td> 8-12周，25-30G </td><td>男，捐助者或收件人</td></tr></tbody></table> 表2。小鼠的表，注明IC试剂和设备。

development of obliterative bronchiolitis in a murine model of orthotopic lung transplantation

首先报道于1971年1 Asimacopoulos和同事在大鼠原位肺移植。目前，这种方法是很好的接受和标准化不仅为异体排斥反应的研究，而且也为研究肺移植后缺血再灌注损伤的机制之间的同源菌株。虽然老鼠和其他大型动物模型2的应用显着澄清这些研究，这些调查的范围是有限的敲除和转基因大鼠的稀缺。由于没有有效的治疗闭塞性细支气管炎，肺移植患者死亡的首要原因，出现了一个密集的搜索，复制闭塞性细支气管炎的临床前模型。气管移植模型是使用最广泛的，可能会重现一些闭塞性细支气管炎的病理特点3。然而，缺乏一个完整的vasculat余吕杏茜没有连接到收件人的传导性气道，不完全闭塞性细支气管炎的病理特点限制了这种模式4的效用。不同于其他固体器官移植，血管小鼠肺移植仅在最近才报道由冈崎和他的同事在2007年5月首次。我们的实验室应用的大鼠肺移植的基本原则，发起闭塞性细支气管炎模型，利用未成年人histoincompatible抗原小鼠原位左单肺移植手术，让6闭塞性细支气管炎的免疫病理的进一步研究。

Watch this Scientific Journal Video about Development of Obliterative Bronchiolitis in a Murine Model of Orthotopic Lung Transplantation at JoVE.com

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

闭塞性细支气管炎，肺移植受者长期存活的主要障碍和缺乏一个强有力的临床前模型排除闭塞性细支气管炎免疫病理检查。不同于其他实体器官移植，肺移植血管鼠标只有最近开发。在这里，我们显示我们独立开发的闭塞性细支气管炎模型小鼠原位单肺移植后。

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 ...

development-obliterative-bronchiolitis-murine-model-orthotopic-lung

Research

JoVE Journal

Medicine

20.1K 次观看.  Indiana University School of Medicine. 闭塞性细支气管炎，肺移植受者长期存活的主要障碍和缺乏一个强有力的临床前模型排除闭塞性细支气管炎免疫病理检查。不同于其他实体器官移植，肺移植血管鼠标只有最近开发。在这里，我们显示我们独立开发的闭塞性细支气管炎模型小鼠原位单肺移植后。

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

Orthotopic Aortic Transplantation: A Rat Model to Study the Development of Chronic Vasculopathy

Research models of chronic rejection are essential to investigate pathobiological and pathophysiological processes during the development of transplant vasculopathy (TVP).
The commonly used animal model for cardiovascular chronic rejection studies is the heterotopic heart transplant model performed in laboratory rodents. This model is used widely in experiments since Ono and Lindsey (3) published their technique. To analyze the findings in the blood vessels, the heart has to be sectioned and all vessels have to be measured.
Another method to investigate chronic rejection in cardiovascular questionings is the aortic transplant model (1, 2). In the orthotopic aortic transplant model, the aorta can easily be histologically evaluated (2). The PVG-to-ACI model is especially useful for CAV studies, since acute vascular rejection is not a major confounding factor and Cyclosporin A (CsA) treatment does not prevent the development of CAV, similar to what we find in the clinical setting (4). A7-day period of CsA is required in this model to prevent acute rejection and to achieve long-term survival with the development of TVP.
This model can also be used to investigate acute cellular rejection and media necrosis in xenogeneic models (5).

This video demonstrates the orthotopic aortic transplant model as a simple model to study the development of transplant vasculopathy (TVP) in rats.

主动脉原位移植大鼠模型，研究慢性血管病变的发展

Research models of chronic rejection are essential to investigate pathobiological and pathophysiological processes during the development of transplant ...

科研

医学

An Orthotopic Model of Murine Bladder Cancer

In this straightforward procedure, bladder tumors are established in female C57 mice through the use of catheterization, local cauterization, and subsequent cell adhesion. After their bladders are transurethrally catheterized and drained, animals are again catheterized to permit insertion of a platinum wire into bladders without damaging the urethra or bladder. The catheters are made of Teflon to serve as an insulator for the wire, which will conduct electrical current into the bladder to create a burn injury. An electrocautery unit is used to deliver 2.5W to the exposed end of the wire, burning away extracellular layers and providing attachment sites for carcinoma cells that are delivered in suspension to the bladder through a subsequent catheterization. Cells remain in the bladder for 90 minutes, after which the catheters are removed and the bladders allowed to drain naturally. The development of tumor is monitored via ultrasound. Specific attention is paid to the catheterization technique in the accompanying video.

Bladder tumors are established in female mice in a minimally invasive fashion through catheterization, local cauterization, and subsequent adhesion of carcinoma cells to the burn sites.

一个小鼠膀胱癌原位模型

In this straightforward procedure, bladder tumors are established in female C57 mice through the use of catheterization, local cauterization, and ...

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 ...

Surgical Procedures for a Rat Model of Partial Orthotopic Liver Transplantation with Hepatic Arterial Reconstruction

Orthotopic liver transplantation (OLT) in rats using a whole or partial graft is an indispensable experimental model for transplantation research, such as studies on graft preservation and ischemia-reperfusion injury 1,2, immunological responses 3,4, hemodynamics 5,6, and small-for-size syndrome 7. The rat OLT is among the most difficult animal models in experimental surgery and demands advanced microsurgical skills that take a long time to learn. Consequently, the use of this model has been limited. Since the reliability and reproducibility of results are key components of the experiments in which such complex animal models are used, it is essential for surgeons who are involved in rat OLT to be trained in well-standardized and sophisticated procedures for this model.
While various techniques and modifications of OLT in rats have been reported 8 since the first model was described by Lee et al. 9 in 1973, the elimination of the hepatic arterial reconstruction 10 and the introduction of the cuff anastomosis technique by Kamada et al. 11 were a major advancement in this model, because they simplified the reconstruction procedures to a great degree. In the model by Kamada et al., the hepatic rearterialization was also eliminated. Since rats could survive without hepatic arterial flow after liver transplantation, there was considerable controversy over the value of hepatic arterialization. However, the physiological superiority of the arterialized model has been increasingly acknowledged, especially in terms of preserving the bile duct system 8,12 and the liver integrity 8,13,14.
In this article, we present detailed surgical procedures for a rat model of OLT with hepatic arterial reconstruction using a 50% partial graft after ex vivo liver resection. The reconstruction procedures for each vessel and the bile duct are performed by the following methods: a 7-0 polypropylene continuous suture for the supra- and infrahepatic vena cava; a cuff technique for the portal vein; and a stent technique for the hepatic artery and the bile duct.

Orthotopic liver transplantation in rats is an indispensable experimental model for biomedical research. Here we present our surgical procedures for orthotopic rat liver transplantation with hepatic arterial reconstruction using a 50% partial graft.

部分原位肝移植大鼠模型的肝动脉重建的外科手术

Orthotopic liver transplantation (OLT) in rats using a whole or partial graft is an indispensable experimental model for transplantation research, such as ...

Murine Corneal Transplantation: A Model to Study the Most Common Form of Solid Organ Transplantation

Corneal transplantation is the most common form of organ transplantation in the United States with between 45,000 and 55,000 procedures performed each year. While several animal models exist for this procedure and mice are the species that is most commonly used. The reasons for using mice are the relative cost of using this species, the existence of many genetically defined strains that allow for the study of immune responses, and the existence of an extensive array of reagents that can be used to further define responses in this species. This model has been used to define factors in the cornea that are responsible for the relative immune privilege status of this tissue that enables corneal allografts to survive acute rejection in the absence of immunosuppressive therapy. It has also been used to define those factors that are most important in rejection of such allografts. Consequently, much of what we know concerning mechanisms of both corneal allograft acceptance and rejection are due to studies using a murine model of corneal transplantation. In addition to describing a model for acute corneal allograft rejection, we also present for the first time a model of late-term corneal allograft rejection.

Mice have been used as a model for studying many forms of transplantation, including corneal transplantation. We describe in this report a murine model for both acute and late-term corneal transplantation.

小鼠角膜移植模型，研究实体器官移植的最常见形式

Corneal transplantation is the most common form of organ transplantation in the United States with between 45,000 and 55,000 procedures performed each ...

Method of Isolated Ex Vivo Lung Perfusion in a Rat Model: Lessons Learned from Developing a Rat EVLP Program

The number of acceptable donor lungs available for lung transplantation is severely limited due to poor quality. Ex-Vivo Lung Perfusion (EVLP) has allowed lung transplantation in humans to become more readily available by enabling the ability to assess organs and expand the donor pool. As this technology expands and improves, the ability to potentially evaluate and improve the quality of substandard lungs prior to transplant is a critical need. In order to more rigorously evaluate these approaches, a reproducible animal model needs to be established that would allow for testing of improved techniques and management of the donated lungs as well as to the lung-transplant recipient. In addition, an EVLP animal model of associated pathologies, e.g., ventilation induced lung injury (VILI), would provide a novel method to evaluate treatments for these pathologies. Here, we describe the development of a rat EVLP lung program and refinements to this method that allow for a reproducible model for future expansion. We also describe the application of this EVLP system to model VILI in rat lungs. The goal is to provide the research community with key information and &#8220;pearls of wisdom&#8221;/techniques that arose from trial and error and are critical to establishing an EVLP system that is robust and reproducible.

Method of Isolated Ex Vivo Lung Perfusion in a Rat Model: Lessons Learned from Developing a Rat EVLP Program

Ex-Vivo Lung Perfusion (EVLP) has allowed lung transplantation in humans to become more readily available by enabling the ability to assess organs and expand the donor pool. Here, we describe the development of a rat EVLP program and refinements that allow for a reproducible model for future expansion.

的隔离方法<em&gt;离体</em&gt;肺灌注的大鼠模型：教训制定鼠EVLP课程中学

The number of acceptable donor lungs available for lung transplantation is severely limited due to poor quality. Ex-Vivo Lung Perfusion (EVLP) has allowed ...

Pre-clinical Orthotopic Murine Model of Human Prostate Cancer

To study the multifaceted biology of prostate cancer, pre-clinical in vivo models offer a range of options to uncover critical biological information about this disease. The human orthotopic prostate cancer xenograft mouse model provides a useful alternative approach for understanding the specific interactions between genetically and molecularly altered tumor cells, their organ microenvironment, and for evaluation of efficacy of therapeutic regimens. This is a well characterized model designed to study the molecular events of primary tumor development and it recapitulates the early events in the metastatic cascade prior to embolism and entry of tumor cells into the circulation. Thus it allows elucidation of molecular mechanisms underlying the initial phase of metastatic disease. In addition, this model can annotate drug targets of clinical relevance and is a valuable tool to study prostate cancer progression. In this manuscript we describe a detailed procedure to establish a human orthotopic prostate cancer xenograft mouse model.

Prostate cancer is the second most common cause of cancer-related deaths in the United States. An orthotopic cancer model provides a useful approach to understand the biology of prostate cancer and to evaluate the efficacy of therapeutic regimens. This protocol describes detailed steps necessary to establish an orthotopic prostate cancer mouse model.

人前列腺癌的临床前原位小鼠模型

To study the multifaceted biology of prostate cancer, pre-clinical in vivo models offer a range of options to uncover critical biological information ...

Open Tracheostomy Gastric Acid Aspiration Murine Model of Acute Lung Injury Results in Maximal Acute Nonlethal Lung Injury

Acid pneumonitis is a major cause of sterile acute lung injury (ALI) in humans. Acid pneumonitis spans the clinical spectrum from asymptomatic to acute respiratory distress syndrome (ARDS), characterized by neutrophilic alveolitis, and injury to both alveolar epithelium and vascular endothelium. Clinically, ARDS is defined by acute onset of hypoxemia, bilateral patchy pulmonary infiltrates and non-cardiogenic pulmonary edema. Human studies have provided us with valuable information about the physiological and inflammatory changes in the lung caused by ARDS, which has led to various hypotheses about the underling mechanisms. Unfortunately, difficulties determining the etiology of ARDS, as well as a wide range of pathophysiology have resulted in a lack of critical information that could be useful in developing therapeutic strategies.
Translational animal models are valuable when their pathogenesis and pathophysiology accurately reproduce a concept proven in both in vitro and clinical settings. Although large animal models (e.g., sheep) share characteristics of the anatomy of human trachea-bronchial tree, murine models provide a host of other advantages including: low cost; short reproductive cycle lending itself to greater data acquisition; a well understood immunologic system; and a well characterized genome leading to the availability of a variety of gene deletion and transgenic strains. A robust model of low pH induced ARDS requires a murine ALI that targets mainly the alveolar epithelium, secondarily the vascular endothelium, as well as the small airways leading to the alveoli. Furthermore, a reproducible injury with wide differences between different injurious and non-injurious insults is important.
The murine gastric acid aspiration model presented here using hydrochloric acid employs an open tracheostomy and recreates a pathogenic scenario that reproduces the low pH pneumonitis injury in humans. Additionally, this model can be used to examine interaction of a low pH insult with other pulmonary injurious entities (e.g., food particles, pathogenic bacteria).

This protocol induces acute lung injury in a mouse that has close fidelity to the pathogenesis of acid pneumonitis observed in humans. We generate a maximal acute nonlethal low pH lung injury and account for differences in rodent-human anatomic respiratory structure using an open tracheostomy coupled with circumferential pressure release.

急性肺损伤开放气管切开胃酸吸入小鼠模型结果在急性最大非致命性肺损伤

Acid pneumonitis is a major cause of sterile acute lung injury (ALI) in humans. Acid pneumonitis spans the clinical spectrum from asymptomatic to acute ...

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 ...

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 ...