Wright J R, Yang H
Department of Pathology, Izaak Walton Killam-Grace Health Centre, Dalhousie University Faculty of Medicine, Halifax, Nova Scotia, Canada.
Ann Transplant. 1997;2(3):72-5.
Brockmann bodies (BBs), large anatomically discrete islet organs found in some teleost fish, are much more easily harvested than pancreatic islets from mammalian donor sources. Tilapia islets, when transplanted into streptozotocin-diabetic athymic nude mice, will produce long-term normoglycemia and mammalian-like glucose tolerance profiles. Our laboratory has used tilapia BBs as an inexpensive model for studying islet xenograft rejection between discordant species. When transplanted into immunocompetent diabetic mice, tilapia BBs reject in roughly 7-8 days. Results to date suggest that tilapia islets are very immunogenic and that encapsulation is necessary to achieve long-term function in euthymic recipients. Continuous, high-dose immunosuppression using 15-DSG is also effective but causes lethal bone marrow suppression. Less aggressive immunosuppression regimens have achieved only modest prolongation of mean graft survival time. Thus far, immunomodulation techniques and transplantation into immune-privileged sites have been ineffective at prolonging graft survival. Tilapia islets currently represent an excellent, inexpensive donor source for discordant islet xenotransplantation studies. In the not distant future, encapsulated islets harvested from transgenic tilapia bearing humanized tilapia insulin genes may also play a role in establishing clinical islet xenotransplantation as a useful treatment modality for type I diabetes mellitus.
布罗克曼体（BBs）是在一些硬骨鱼中发现的大型解剖学上离散的胰岛器官，比从哺乳动物供体来源获取的胰腺胰岛更容易收获。罗非鱼胰岛移植到链脲佐菌素诱导的糖尿病无胸腺裸鼠体内时，会产生长期正常血糖和类似哺乳动物的葡萄糖耐量曲线。我们实验室已将罗非鱼BBs作为一种廉价模型，用于研究异种胰岛移植在不同物种间的排斥反应。当移植到具有免疫活性的糖尿病小鼠体内时，罗非鱼BBs大约在7 - 8天内被排斥。迄今为止的结果表明，罗非鱼胰岛具有很强的免疫原性，并且包封对于在有胸腺受体中实现长期功能是必要的。使用15 - DSG进行持续高剂量免疫抑制也有效，但会导致致命的骨髓抑制。不太激进的免疫抑制方案仅适度延长了平均移植物存活时间。到目前为止，免疫调节技术和移植到免疫豁免部位在延长移植物存活方面均无效。罗非鱼胰岛目前是异种胰岛移植研究中一种优秀且廉价的供体来源。在不久的将来，从携带人源化罗非鱼胰岛素基因的转基因罗非鱼中收获的包封胰岛，可能也会在将临床胰岛异种移植确立为I型糖尿病的一种有效治疗方式中发挥作用。
