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气管同种异体移植成分的抗原性评估及免疫抑制方案在啮齿动物模型中的作用

Evaluation of Antigenicity of Components of Tracheal Allotransplant and Effect of Immunosuppressant Regime in a Rodent Model.

作者信息

Sharma Dimpy, Iyer Subramania, Subramaniam Sobha, Ramu Janarthanan, Sharma Mohit, Nambiar Ajit, Unni Akk, S Sivanarayanan

机构信息

Department of Plastic and Reconstructive Surgery, Amrita Institute of Medical Sciences and Research Centre, Kochi, Kerala, India.

Department of Head and Neck Surgical Oncology, Amrita Institute of Medical Sciences and Research Centre, Kochi, Kerala, India.

出版信息

Indian J Plast Surg. 2020 Dec;53(3):357-362. doi: 10.1055/s-0040-1721860. Epub 2020 Dec 21.

DOI:10.1055/s-0040-1721860
PMID:33402765
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC7775257/
Abstract

Tracheal transplantation seems to be the logical step in the process of reconstruction of the trachea following a long-segment resection, which is usually done to treat malignant disease or benign stenosis of the airway caused by a traumatic, congenital, inflammatory, or iatrogenic lesion. Immunosuppression following transplant is essential but not ideal after oncoresection.  The tracheal allografts, harvested from Sprague Dawley rats, were implanted in the Wistar strain rat. The harvested tracheal grafts were divided into groups and subgroups, based on the layers of trachea, method of decellularization, and immunosuppression. The antigenicity of different layers of trachea and the effect of various decellularization methods were studied within three time frames, that is, day 3, 9, and 15.  On structural analysis, the day 3 and day 15 samples showed no meaningful comparison could be made, due to extensive neutrophil infiltration in all three layers. The day 9 tracheal grafts showed loss of epithelium, with no signs of regeneration in most of the allografts. The subepithelial lymphoid infiltration was found to be severe in nonimmunosuppressed allografts. The group in which both inner and outer layers were removed showed moderate-to-severe infiltrate of lymphoid cells in all the allografts, but there was no cartilage loss, irrespective of the method of decellularization. The irradiated specimens retained the cartilage but showed extensive ischemic damage.  Rat trachea is a good model for tracheal transplant research but not adequately sturdy to sustain mechanical debridement. Irradiation and chemical decellularization eliminates the immune response but causes intense ischemic damage. Out of the three time frames, day 9 seemed to be the best to study the immune response. To substantiate the results obtained in this study, the immunohistochemical study of the allografts is needed to be performed among a larger group of animals.

摘要

气管移植似乎是长段气管切除术后气管重建过程中的合理步骤,长段气管切除通常用于治疗由创伤、先天性、炎症性或医源性病变引起的气道恶性疾病或良性狭窄。移植后的免疫抑制至关重要,但肿瘤切除术后并不理想。从Sprague Dawley大鼠获取的气管同种异体移植物被植入Wistar品系大鼠体内。根据气管层次、去细胞方法和免疫抑制情况,将获取的气管移植物分为不同的组和亚组。在三个时间点,即第3天、第9天和第15天,研究气管不同层次的抗原性以及各种去细胞方法的效果。在结构分析方面,第3天和第15天的样本由于所有三层均有广泛的中性粒细胞浸润,无法进行有意义的比较。第9天的气管移植物显示上皮细胞缺失,大多数同种异体移植物没有再生迹象。在未进行免疫抑制的同种异体移植物中,发现上皮下淋巴浸润严重。内外层均被去除的组中,所有同种异体移植物均显示淋巴细胞中度至重度浸润,但无论去细胞方法如何,均无软骨丢失。照射后的标本保留了软骨,但显示出广泛的缺血损伤。大鼠气管是气管移植研究的良好模型,但不够坚固,无法承受机械清创。照射和化学去细胞可消除免疫反应,但会导致严重的缺血损伤。在这三个时间点中,第9天似乎是研究免疫反应的最佳时间。为了证实本研究获得的结果,需要在更大数量的动物中对同种异体移植物进行免疫组织化学研究。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5890/7775257/2a0437b7cd25/10-1055-s-0040-1721860_6_0527_07.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5890/7775257/d25fa96b8a5b/10-1055-s-0040-1721860_6_0527_01.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5890/7775257/fcb6a4629f58/10-1055-s-0040-1721860_6_0527_02.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5890/7775257/d8468de10ba1/10-1055-s-0040-1721860_6_0527_03.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5890/7775257/64eb6c75b63c/10-1055-s-0040-1721860_6_0527_04.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5890/7775257/3b6b5705372c/10-1055-s-0040-1721860_6_0527_05.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5890/7775257/5f39eb2459d7/10-1055-s-0040-1721860_6_0527_06.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5890/7775257/2a0437b7cd25/10-1055-s-0040-1721860_6_0527_07.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5890/7775257/d25fa96b8a5b/10-1055-s-0040-1721860_6_0527_01.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5890/7775257/fcb6a4629f58/10-1055-s-0040-1721860_6_0527_02.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5890/7775257/d8468de10ba1/10-1055-s-0040-1721860_6_0527_03.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5890/7775257/64eb6c75b63c/10-1055-s-0040-1721860_6_0527_04.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5890/7775257/3b6b5705372c/10-1055-s-0040-1721860_6_0527_05.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5890/7775257/5f39eb2459d7/10-1055-s-0040-1721860_6_0527_06.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5890/7775257/2a0437b7cd25/10-1055-s-0040-1721860_6_0527_07.jpg

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