Marcheix Bertrand, Yacoub-Youssef Houda, Calise Denis, Thiers Jean-Claude, Therville Nicole, Benoist Hervé, Blaes Nelly, Ségui Bruno, Game Xavier, Dambrin Camille, Thomsen Mogens
INSERM U466, University Hospital Rangeuil, Toulouse, France.
J Heart Lung Transplant. 2006 Jun;25(6):675-82. doi: 10.1016/j.healun.2006.01.005. Epub 2006 May 2.
Chronic vascular rejection (CVR) is a major problem in clinical transplantation. Studies in experimental animals have been important to understand some of its mechanisms, but they are hampered by the difficulty of extrapolating the results into clinical practice.
We created a new experimental model for the study of human CVR by grafting multiple human mesenteric arteries from the same human donor into different SCID/beige mice in the infrarenal aortic position. Twenty-seven different mice were successfully grafted with a human artery from 6 donors. One week later, 23 of the mice received an intraperitoneal injection of 40 million human spleen cells, either from the same donor (autologous) or from another donor (allogeneic).
In 81% of the mice an immune reconstitution was obtained, shown by the presence of human T, B and NK cells and IgG in circulating blood. At the time of sacrifice, 5 weeks after the arterial transplantation, a typical CVR with infiltration of human immune cells and deposit of human immunoglobulin was observed in the reconstituted mice that received allogeneic cells, whereas only minor lesions were noted in autologous combinations. No CVR was observed without injection of human splenocytes. We did not observe lymphoma or graft-vs-host reactions during the experiment.
We show that it is feasible to graft multiple human arteries from the same donor into SCID/beige mice, and that a specific and typical CVR is observed after reconstitution with allogeneic spleen cells. Our method allows for pre-clinical testing of new therapeutics in controlled series.
慢性血管排斥反应（CVR）是临床移植中的一个主要问题。对实验动物的研究对于理解其一些机制很重要，但将结果外推至临床实践存在困难，这阻碍了相关研究。
我们通过将来自同一人类供体的多根人肠系膜动脉移植到不同的SCID/米色小鼠的肾下主动脉位置，创建了一种用于研究人类CVR的新实验模型。27只不同的小鼠成功移植了来自6名供体的人动脉。一周后，23只小鼠接受了腹腔注射4000万个人脾细胞，这些脾细胞要么来自同一供体（自体），要么来自另一个供体（异体）。
81%的小鼠实现了免疫重建，循环血液中出现了人类T细胞、B细胞、NK细胞和IgG。在动脉移植5周后的处死时，在接受异体细胞的重建小鼠中观察到典型的CVR，伴有人类免疫细胞浸润和人类免疫球蛋白沉积，而自体组合中仅发现轻微病变。未注射人脾细胞时未观察到CVR。实验期间未观察到淋巴瘤或移植物抗宿主反应。
我们表明将来自同一供体的多根人动脉移植到SCID/米色小鼠中是可行的，并且在用异体脾细胞重建后可观察到特异性和典型的CVR。我们的方法允许在可控系列中对新疗法进行临床前测试。
