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猪睾丸内胰岛在未免疫抑制的比格犬体内的长期存活

Long-term survival of intratesticular porcine islets in nonimmunosuppressed beagles.

作者信息

Gores Paul F, Hayes Daniel H, Copeland M Jane, Korbutt Gregory S, Halberstadt Craig, Kirkpatrick Shaun A, Rajotte Ray V

机构信息

Department of Surgery, Carolinas Medical Center, Charlotte, NC, USA.

出版信息

Transplantation. 2003 Mar 15;75(5):613-8. doi: 10.1097/01.TP.0000052376.89400.8D.

DOI:10.1097/01.TP.0000052376.89400.8D
PMID:12640298
Abstract

BACKGROUND

The testis is an immunoprivileged organ, and at 37 degrees C, the intratesticular microenvironment supports the survival of allogeneic islets. The objective of this study was to determine whether the immunoprotection afforded by the intratesticular environment is potent enough to prevent the rejection of xenogeneic porcine islets in a large-animal model.

METHODS

A bilateral cryptorchid condition was surgically created in sexually mature beagle dogs. Porcine islets were prepared from neonatal pigs by collagenase digestion and 9 days of culture, after which they were injected into each of the cryptorchid testes. Control dogs received liver subcapsular space transplants of porcine islets and autologous islets. After 100 days, the testes and relevant portions of liver were studied immunohistochemically for the presence of islet tissue.

RESULTS

The testicular interstitial space of all dogs contained abundant islet tissue. No evidence of lymphocytic infiltration or inflammation was observed. In contrast, porcine islets transplanted to the liver subcapsular space do not survive, although autologous islets engraft well in that position. This occurs even though the recipient's serum contains preformed cytotoxic antibodies to porcine islets that persist after transplantation.

CONCLUSIONS

These results demonstrate that the microenvironment existing within the surgically repositioned intra-abdominal testis supports the survival of xenogeneic tissue. The survival of xenogeneic tissue in the absence of immunosuppression in this large-animal model raises the possibility that xenogeneic porcine islet tissue will also survive in humans if transplanted into a similar environment.

摘要

背景

睾丸是一个免疫赦免器官,在37摄氏度时,睾丸内微环境支持同种异体胰岛的存活。本研究的目的是确定睾丸内环境提供的免疫保护是否强大到足以在大型动物模型中防止异种猪胰岛被排斥。

方法

通过手术在性成熟的比格犬身上制造双侧隐睾情况。通过胶原酶消化和9天培养从新生猪制备猪胰岛,之后将其注入每个隐睾睾丸。对照犬接受猪胰岛和自体胰岛的肝包膜下间隙移植。100天后,对睾丸和肝脏的相关部分进行免疫组织化学研究,以检测胰岛组织的存在。

结果

所有犬的睾丸间质空间都含有丰富的胰岛组织。未观察到淋巴细胞浸润或炎症迹象。相比之下,移植到肝包膜下间隙的猪胰岛无法存活,尽管自体胰岛在该位置能良好植入。即使受体血清中含有移植后持续存在的针对猪胰岛的预先形成的细胞毒性抗体,这种情况仍会发生。

结论

这些结果表明,手术重新定位的腹腔内睾丸内存在的微环境支持异种组织的存活。在这个大型动物模型中,异种组织在没有免疫抑制的情况下存活,这增加了如果将异种猪胰岛组织移植到类似环境中在人类体内也能存活的可能性。

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