Orthotopic tracheal transplantation in the murine model

Orthotopic tracheal transplantation in the murine model
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DOI:
10.1097/00007890-200205150-00010
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发表时间:
2002-05-15
期刊:
影响因子:
6.2
通讯作者:
Mayer, L
Mayer, L
中科院分区:
医学2区
文献类型:
--
作者:
Genden, EM;Boros, P;Mayer, L

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背景在气管移植可以在临床上应用于重建危及生命的气道缺损之前,必须更好地表征该器官系统的免疫生物学。试剂和转基因小鼠品系的可用性使得鼠模型成为该目的的理想选择。我们已经开发了一种可靠的和可重复的原位气管移植方法,并表征了排斥反应的动力学。Balb/c供体气管段(5个气管环)原位移植到同基因Balb/c受体或异基因C57 BL/6受体中。通过每日临床气道评估、体内纤毛运动、苏木精-伊红染色和CD 8/CD 4免疫组化进行组织学检查来监测气管移植物排斥反应。气管移植后两天,同种异体受体出现持续性可闻喘鸣,而同基因实验组未出现。而同基因气管自体移植物移植后表现出正常的纤毛功能,异基因受体未能实现正常的纤毛功能。正常的组织结构持续在同基因移植物没有淋巴细胞浸润的证据;然而,非免疫抑制同种异体移植物表现出正常纤毛呼吸道上皮细胞和CD 8/CD 4阳性淋巴细胞浸润的损失,在移植后21天达到高峰。Balb/c(供体)-C57 BL/6(受体)小鼠原位气管移植模型为研究气管移植提供了可靠的方法。
Background. Before tracheal transplantation can be clinically applied for the reconstruction of life-threatening airway defects, the immunobiology of this organ system must be better characterized. The availability of reagents and transgenic mice strains make the murine model ideal for this purpose. We have developed a reliable and reproducible method of orthotopic tracheal transplantation and characterized the kinetics of rejection.Methods. Balb/c donor tracheal segments (five tracheal rings), were orthotopically transplanted into either syngeneic Balb/c recipients or allogeneic C57BL/6 recipients. Tracheal graft rejection was monitored by daily clinical airway assessment, in vivo cilia motility, and histologic examination using hematoxylin and eosin staining and CD8/CD4 immunohistochemistry.Results. Two days after tracheal transplantation, allogenic recipients developed a persistent audible stridor that did not occur in the syngeneic experimental group. Whereas syngeneic tracheal autografts demonstrated normal mucociliary function after transplantation, allogeneic recipients failed to achieve normal mucociliary function. Normal histologic architecture persisted in the syngeneic grafts without evidence of lymphocytic infiltrate; however, the nonimmunosuppressed allogeneic grafts demonstrated a loss of normal ciliated respiratory epithelia and a CD8/CD4-positive lymphocytic infiltrate that peaked at 21 days after transplantation.Conclusions. The Balb/c (donor) to C57BL/6 (recipient) murine orthotopic tracheal transplant model offers a reliable method for the study of tracheal transplantation.