Establishment of a mouse-rat cervical cardiac xenotransplantation model by cuff technique

doi:10.3969/j.issn.2095-4344.2013.05.015

Abstract

Abstract:

BACKGROUND: Small animal heart transplantation model is a common model and an important mean for basic and clinical research of organ transplantation, and the transplant part is often the neck and abdomen. The biggest advantage of cervical heterotopic transplantation is that the transplanted heart will located in the neck subcutaneous, which is conducive to the direct observation of the beating of donor heart, thus early anticipating the rejection.
OBJECTIVE: To improve the anesthesia, surgical procedures and perioperative management of the mouse-rat cervical cardiac xenotransplantation model, in order to establish a more stable animal model.
METHODS: The mouse-rat heterotopic cardiac xenotransplantation models were established by modified cuff technique to transfer the donor heart of mouse to the right side of the neck of rat, the method to remove the donor heart was improved, and the models received inhalation anesthesia of isoflurane with small animal anesthesia machine. The experimental levels of establishing the models were divided into practicing, stable and skilled stages. Part samples were taken for the histopathological examination.
RESULTS AND CONCLUSION: In the three stages (practicing, stable, skilled) of establishing the models, the successful rates of surgery were 53.33%, 85.71%, and 96.15% respectively. The successful rate in stable and skilled stages was higher than that in the practicing stage (P < 0.05). The total operation time in the stable and skilled stages was significantly shorter than that in the practicing stage (P < 0.05). Histopathological examination results showed that the cardiovascular endothelial injury, thrombosis, myocardial parenchymal damage, interstitial hemorrhage and inflammatory cell infiltration after heterotopic cardiac xenotransplantation were more serious compared with normal heart transplantation and cardiac allograft, and showed a time-depend manner, which identify the reliability of the model. It suggests that the mouse-rat cervical cardiac xenotransplantation model is simple, reliable, easily operated in a short-time and has a high successful rate. It is an ideal animal model for studying xenotransplantation rejection.

Key words: organ transplantation, heart-lung transplantation, cardiac xenotransplantation, mice, rats, animal models, ectopic, cuff method, rejection, the National Natural Science Foundation of China, photographs-containing paper of organ transplantation

CLC Number:

R318

Li Chuan, Qi Feng, Liu Tong, Li Fu-xin, Wang Peng-zhi. Establishment of a mouse-rat cervical cardiac xenotransplantation model by cuff technique[J]. Chinese Journal of Tissue Engineering Research, 2013, 17(5): 859-865.

Figures/Tables 6

References

[1] Zhou S, Peng LK, Xie XB, et al. Zhongguo Zuzhi Gongcheng Yanjiu yu Linchuang Kangfu. 2010;14(44):8283-8287.周松,彭龙开,谢续标,等. 异种器官移植的研究进展[J]. 中国组织工程研究与临床康复,2010,14(44):8283-8287.

[2] Dou KF, Li X, Li JJ, et al. Zhonghua Qiguan Yizhi Zazhi. 2012; 33(3):184-188.窦科峰,李霄,李俊杰,等. 异种器官移植研究的主要问题与对策[J]. 中华器官移植杂志,2012,33(3):184-188.

[3] Chu J, Yu YB, Zhang SH, et al. Shandong Yiyao. 2011;51(44): 112-113.储建,禹亚彬,章世海,等. 异种器官移植的研究进展[J]. 山东医药,2011,51(44):112-113.

[4] Mendicino M, Liu M, Ghanekar A, et al. Targeted deletion of Fgl-2/fibroleukin in the donor modulates immunologic response and acute vascular rejection in cardiac xenografts. Circulation. 2005;112(2):248-256.

[5] Hosiawa KA, Wang H, Devries ME, et al. CD80/CD86 costimulation regulates acute vascular rejection. J Immunol. 2005;175(9):6197-6204.

[6] Won JY, Ahn KS, Sorrell AM, et al. Cytolytic assessment of hyperacute rejection and production of nuclear transfer embryos using hCD46-transgenic porcine embryonic germ cells. Zygote. 2009;17(2):101-108.

[7] Liu B, Cheng C, Wu Y, et al. Transgenic mice designed to express human alpha-1,2-fucosyltransferase in combination of human DAF and CD59 to avoid xenograft rejection. Sci China C Life Sci. 2008;51(3):199-204.

[8] Su S. Zhonghua Qiguan Yizhi Zazhi. 2007;28(4):251-252.苏松. 小鼠器官移植模型的现状和展望[J]. 中华器官移植杂志,2007,28(4):251-252.

[9] Tao R, Wang L, Han R, et al. Differential effects of B and T lymphocyte attenuator and programmed death-1 on acceptance of partially versus fully MHC-mismatched cardiac allografts. J Immunol. 2005;175(9):5774-5782.

[10] Tomita Y, Zhang QW, Matsuzaki G, et al. Absent mRNA accumulation of Th1 or Th2 cytokines in heart allografts with chimerism-based drug-induced tolerance. Surg Today. 2005; 35(5):364-370.

[11] Qi F, Zhu LW, He XH, et al. Tianjin Yike Daxue Xuebao. 2010; 16(4):559-562.戚峰,朱理玮,何向辉,等. 多靶点联合用药抑制小鼠到大鼠异种心脏移植排斥反应[J]. 天津医科大学学报,2010,16(4):559-562.

[12] Cooper DK, Teuteberg JJ. Pig heart xenotransplantation as a bridge to allotransplantation. J Heart Lung Transplant. 2010; 29(8):838-840.

[13] Manji RA, Menkis AH, Cooper DK. Cardiac xenotransplantation technology provides materials for improved bioprosthetic heart valves. J Thorac Cardiovasc Surg. 2011;142(1):238-239, 239.

[14] Huang XS, Liu X, Chen DZ, et al. Zhongguo Xiufu Chongjian Waike Zazhi. 2005;19(7):583-586.黄雪珊,刘璇,陈道中,等. 改良Heron法建立异种异位心脏移植模型[J]. 中国修复重建外科杂志,2005,19(7):583-586.

[15] Tang H, Yao ZX, Liu SC, et al. Zhongguo Xiandai Yixue Zazhi. 2008;18(1):21-24.唐华,姚榛祥,刘盛春,等. 鼠异种异位心脏移植模型建立与病理特征观察[J]. 中国现代医学杂志,2008,18(1):21-24.

[16] Wei L, Wang M, Qu X, et al. Differential expression of microRNAs during allograft rejection. Am J Transplant. 2012; 12(5):1113-1123.

[17] Chen WW, Yang YR, Xia P, et al. Wenzhou Yixueyuan Xuebao. 2011;41(3):252-254.陈文伟,杨亦荣,夏鹏,等. 小鼠颈部异位心脏移植手术的改良[J]. 温州医学院学报,2011,41(3):252-254.

[18] Wang JX, Huang SD, Xu ZY, et al. Tongji Daxue Xuebao. 2008; 29(1):106-108.王建雄,黄盛东,徐志云,等. 改良移植技术建立豚鼠至大鼠异位心脏移植模型[J]. 同济大学学报: 医学版, 2008,29(1):106-108.

[19] Zhang SL, Sun ZQ. Zhongguo Zuzhi Gongcheng Yanjiu yu Linchuang Kangfu. 2010;14(31):5883-5886.张松林,孙宗全. 应用Tail-cuff技术改良小鼠颈部异位心脏移植模型[J]. 中国组织工程研究与临床康复, 2010,14(31): 5883-5886.

[20] Postrach J, Bauer A, Schmoeckel M, et al. Heart xenotransplantation in primate models. Methods Mol Biol. 2012;885:155-168.

[21] Choi HJ, Kim MK, Lee HJ, et al. Effect of alphaGal on corneal xenotransplantation in a mouse model. Xenotransplantation. 2011;18(3):176-182.

[22] Hawthorne WJ, Simond DM, Stokes R, et al. Pre-clinical model of composite foetal pig pancreas fragment/renal xenotransplantation to treat renal failure and diabetes. Xenotransplantation. 2011;18(6):390-399.

[23] Luca G, Calvitti M, Mancuso F, et al. Reversal of experimental Laron Syndrome by xenotransplantation of microencapsulated porcine Sertoli cells. J Control Release. 2012.

[24] Li C, Luo L, Lu J, et al. A modified splint tubing technique for heterotopic heart transplantation in mouse. Transpl Immunol. 2011;25(1):82-87.

[25] Jiang XF, Zhu L, Cui ZM, et al. Zhongguo Puwai Jichu yu Linchuang Zazhi. 2010;17(9):914-916.姜晓峰,朱磊,崔哲铭,等. 一种改良的吻合法小鼠腹腔异位心脏移植模型[J]. 中国普外基础与临床杂志,2010,17(9):914-916.

[26] Yan GF, Zhang J, Zhou Y, et al. Shiyan Dongwu yu Bijiao Yixue. 2008;28(5):341-342.严国锋,张健,周勇,等. 保温措施对小鼠麻醉效果的影响[J]. 实验动物与比较医学,2008,28(5):341-342.

[27] Hansen TN, Haworth RA, Southard JH. Warm and cold ischemia result in different mechanisms of injury to the coronary vasculature during reperfusion of rat hearts. Transplant Proc. 2000;32(1):15-18.

[28] Li S, Guan Q, Chen Z, et al. Reduction of cold ischemia-reperfusion injury by graft-expressing clusterin in heart transplantation. J Heart Lung Transplant. 2011;30(7): 819-826.

[29] Brenner P, Keller M, Beiras-Fernandez A, et al. Prevention of hyperacute xenograft rejection through direct thrombin inhibition with hirudin. Ann Transplant. 2010;15(4):30-37.

[30] Schumacher M, Van Vliet BN, Ferrari P. Kidney transplantation in rats: an appraisal of surgical techniques and outcome. Microsurgery. 2003;23(4):387-394.