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成功实现猪同种异体气管移植物的免疫抑制剂-free 异位移植。

Successful immunosuppressant-free heterotopic transplantation of tracheal allografts in the pig.

机构信息

Department of Thoracic Surgery, CHU Lille, Lille, France.

Environnement Périnatal et Santé (EA 4489), Université Lille, Lille, France.

出版信息

Eur J Cardiothorac Surg. 2017 Aug 1;52(2):248-255. doi: 10.1093/ejcts/ezx116.

DOI:10.1093/ejcts/ezx116
PMID:28472471
Abstract

OBJECTIVES

It has been demonstrated that both heterotopic and orthotopic transplants of epithelium-denuded cryopreserved tracheal allografts are feasible in immunosuppressant-free rabbits. Validation of these results in large animals is required before considering clinical applications. We evaluated the viability, immune tolerance and strain properties of such tracheal allografts heterotopically transplanted in a pig model.

METHODS

Ten tracheal segments, 5 short (5 rings) and 5 long (10 rings), were obtained from male Landrace pigs. The tracheal segments were surgically denuded of their epithelium, then cryopreserved and stored in a tissue bank for 33 to 232 days. After thawing, tracheal segments stented with a silicone tube were wrapped in the omentum in 2 groups of 5 female recipients. The animals did not receive any immunosuppressive drugs. The animals were euthanized from Day 6 to Day 90 in both groups.

RESULTS

An effective revascularization of allografts regardless of length was observed. Lymphocyte infiltrate was shown in the early postoperative period and became non-significant after 30 days. Allografts displayed high levels of neoangiogenesis and viable cartilage rings with islets of calcification. Biomechanical measurements demonstrated strain properties similar to those of a fresh tracheal segment from Day 58.

CONCLUSIONS

Our results demonstrate the acceptability and satisfactory stiffness of epithelium-denuded cryopreserved tracheal allografts implanted in the omentum, despite the absence of immunosuppressive drugs. Since the omentum has the capability to reach the tracheal region, this approach should be investigated in the setting of orthotopic transplants in a pig model before considering clinical applications.

摘要

目的

已证实,去上皮的冷冻保存同种异体气管移植物的异位和原位移植在无免疫抑制剂的兔中是可行的。在考虑临床应用之前,需要在大动物中验证这些结果。我们评估了这种在猪模型中异位移植的去上皮冷冻保存同种异体气管移植物的存活率、免疫耐受性和种属特性。

方法

从雄性长白猪获得 10 个气管段,5 个短(5 个环)和 5 个长(10 个环)。气管段经手术去上皮,然后冷冻保存并在组织库中储存 33 至 232 天。解冻后,用硅胶管支撑的气管段被包裹在网膜中,在 2 组 5 只雌性受体内。动物没有接受任何免疫抑制剂。两组动物均在第 6 天至第 90 天被安乐死。

结果

观察到所有移植物的有效再血管化,与长度无关。术后早期可见淋巴细胞浸润,30 天后不再显著。同种异体移植物显示出高水平的新生血管形成和有活软骨环的钙化岛。生物力学测量显示,从第 58 天起,应变特性与新鲜气管段相似。

结论

我们的结果表明,在没有免疫抑制剂的情况下,植入网膜中的去上皮冷冻保存同种异体气管移植物是可以接受的,并且具有令人满意的刚度。由于网膜有到达气管区域的能力,在考虑临床应用之前,应该在猪模型的原位移植中对此方法进行研究。

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Successful immunosuppressant-free heterotopic transplantation of tracheal allografts in the pig.成功实现猪同种异体气管移植物的免疫抑制剂-free 异位移植。
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