Gerber H, Wagner H E, Bürgi U, Peter H J
Department of Clinical Chemistry, University of Bern School of Medicine, Inselspital, Switzerland.
Exp Clin Endocrinol Diabetes. 1996;104 Suppl 3:56-9. doi: 10.1055/s-0029-1211688.
Since Shimosato et al., in the mid 70s transplanted for the first time thyroid carcinoma tissue onto nude mice, other research groups have made use of the nude mouse model for the investigation of xenotransplanted thyroid tissue. The use of this model for the investigation of benign goiters is briefly discussed in this article. Normal human thyroid tissue has been transplanted either as a control in experiments with benign and malignant goiter tissue, or for the study of thyroid tissue response to stimulators such as TSH or thyroid stimulating antibodies (TSAb). Thyroid glands from 8- to 10-week old human fetuses obtained at the time of legal abortion were cryopreserved in liquid nitrogen and successfully transplanted into nude mice. Moreover, all the variants of human benign goiter tissue have been xenotransplanted: tissue from nodular and diffuse goiters, hot and cold nodules or goiter areas, rapidly growing nodules, etc. Two examples of animal thyroid tissue xenotransplantation onto nude mice are briefly discussed: Nude mice bearing normal thyroid tissue transplants from 4 different species (man, rat, pig, guinea-pig) have been used for the study of the species specific effect of bovine TSH and TSAb. In studies aiming at elucidating the pathogenesis of hyperthyroidism, toxic goiter tissue from hyperthyroid cats has been transplanted. In methodological terms, these experiments have shown that surgically removed goiter tissue can be shipped by air in cell culture medium at 4 degrees C over long distances and then successfully transplanted.-Finally, cell lines such as the rat cell line FRTL-5 can be transplanted onto nude mice either as cell suspension or embedded in collagen, for example for the study of proliferation and folliculogenesis. Using the xenotransplantation model, function and proliferation, morphogenesis and differentiation, as well as thyroid autonomy and response to stimulators have all been studied in xenotransplanted human and animal thyroid thyroid tissue and cell lines under various experimental conditions. Although new research tools, for example transgenic animals, are now increasingly and successfully used, xenotransplantation still offers the possibility of addressing some specific questions which cannot be answered so easily with other experimental models. For example, studies with human tissue, involving drugs or radioactive tracers which cannot be applied to the intact human being, can relatively easily be performed with xenotransplanted human tissue and application of the drug or tracer to the host mouse. Or embryological development can be followed and studied using fetal thyroid (and other) tissue transplanted onto nude mice; here, of course, difficult ethical issues have to be considered. Finally, it should be mentioned that, although many scientific questions can be studied nowadays by cell culture or other in vitro systems, animal models are still needed. Extrapolation to the human being, however, should always be done with caution and we should always keep in mind that for the understanding of a human disease indeed human experimental models remain the goldstandard.
自20世纪70年代中期下里等首次将甲状腺癌组织移植到裸鼠身上以来，其他研究小组已利用裸鼠模型来研究异种移植的甲状腺组织。本文简要讨论了该模型在良性甲状腺肿研究中的应用。正常人类甲状腺组织已被用作良性和恶性甲状腺肿组织实验的对照，或用于研究甲状腺组织对促甲状腺激素（TSH）或甲状腺刺激抗体（TSAb）等刺激物的反应。在合法堕胎时获取的8至10周龄人类胎儿的甲状腺被保存在液氮中，并成功移植到裸鼠体内。此外，人类良性甲状腺肿组织的所有变体都已进行异种移植：来自结节性和弥漫性甲状腺肿、热结节和冷结节或甲状腺肿区域、快速生长结节等的组织。简要讨论了将动物甲状腺组织异种移植到裸鼠身上的两个例子：携带来自4个不同物种（人类、大鼠、猪、豚鼠）正常甲状腺组织移植的裸鼠已被用于研究牛TSH和TSAb的物种特异性作用。在旨在阐明甲状腺功能亢进症发病机制的研究中，已移植了甲状腺功能亢进猫的毒性甲状腺肿组织。从方法学角度来看，这些实验表明，手术切除的甲状腺肿组织可以在4℃的细胞培养基中通过空运远距离运输，然后成功移植。最后，大鼠细胞系FRTL-5等细胞系可以作为细胞悬液或包埋在胶原蛋白中移植到裸鼠身上，例如用于研究增殖和卵泡发生。利用异种移植模型，已在各种实验条件下对异种移植的人类和动物甲状腺组织及细胞系的功能和增殖、形态发生和分化，以及甲状腺自主性和对刺激物的反应进行了研究。尽管现在越来越多地成功使用新的研究工具，例如转基因动物，但异种移植仍然提供了解决一些特定问题的可能性，而这些问题用其他实验模型不容易回答。例如，涉及不能应用于完整人类的药物或放射性示踪剂的人体组织研究，可以相对容易地用异种移植的人体组织进行，并将药物或示踪剂应用于宿主小鼠。或者可以通过将胎儿甲状腺（和其他）组织移植到裸鼠身上来跟踪和研究胚胎发育；当然，这里必须考虑棘手的伦理问题。最后，应该提到的是，尽管现在许多科学问题可以通过细胞培养或其他体外系统进行研究，但动物模型仍然是必需的。然而，向人类的外推应该始终谨慎进行，我们应该始终牢记，为了理解人类疾病，人类实验模型仍然是金标准。
