TRANSPLANTATION OF ENDOCRINE TISSUES

拟议研究的目的是开发方法，使 胰腺和甲状旁腺组织临床移植成功 而不需要免疫抑制治疗。建议进行的研究 这笔赠款的第一部分旨在进一步澄清 客体细胞诱导同种异体免疫的机制。我们正在计划 将甲状腺移植模型和同源小鼠品系用于 结合基因定义的小鼠作为临时宿主。我们 将检验我们的假设，即抗原和共刺激物必须 由一个细胞呈现以刺激对主要疾病的最大反应 组织相容性抗原。在拟议研究的第二部分，我们 正计划将胎儿胰腺组织移植到糖尿病小鼠体内。这个 临时宿主系统将用于耗尽胎鼠胰腺组织 从乘客单元格的内容来看。在高氧气氛中培养会 结合免疫毒素治疗临时宿主。此外, 碳氟化合物将被用来灭活居住在胎儿体内的客体细胞 胰腺组织。提议的方法的新颖性在于 同时使用临时宿主和乘客白细胞去除 治疗方式。在进一步的实验中，人类胎儿胰腺 组织将以类似的方式处理并监测其乘客 白细胞含量将通过使用免疫荧光和 免疫过氧化物酶技术。如果我们应该成功地保存 人胎胰腺组织代谢完整性的同时 能够从客体细胞中耗尽这些组织，我们将继续 该组织移植于青少年起病患者的临床研究 糖尿病。在这些研究的初始阶段，人胎儿胰腺 同时将组织放置在患者的肾被膜下 接受肾移植手术。我们的长期目标是移植人类 非免疫抑制患者的胎儿胰腺组织。第二 临床研究是上述临床研究的延伸。 甲状旁腺移植。人甲状旁腺组织经前处理和 临时宿主将移植给患有医源性和非传染性疾病的患者 先天性甲状旁腺功能减退症。

The purpose of the proposed studies is to develop methods which allow successful clinical transplantation of pancreatic and parathyroid tissue without the need for immunosuppressive therapy. The studies proposed in the first part of this grant are aimed at the further clarification of the mechanism of induction of alloimmunity by passenger cells. We are planning to use the thyroid transplant model and congenic mouse strains in combination with genetically defined mice serving as interim hosts. We will test our hypothesis suggesting that antigen and co-stimulator have to be presented by one cell in order to stimulate a maximal response to major histocompatibility antigens. In the second part of the proposed study, we are planning to transplant fetal pancreatic tissue into diabetic mice. The interim host system will be used to deplete fetal mouse pancreatic tissue from its passenger cell contents. Culture in high oxygen atmosphere will be combined with immunotoxin treatment of the interim host. In addition, fluorocarbon will be used to inactivate passenger cells residing in fetal pancreatic tissue. The novelty of the proposed approach is the simultaneous use of interim hosting and passenger leukocyte depleting treatment modalities. In further experiments, human fetal pancreatic tissue will be treated in a similar manner and monitoring of its passenger leukocyte contents will be performed by the use of immunofluorescence and immunoperoxidase techniques. If we should be successful in preserving the metabolic integrity of human fetal pancreatic tissue and at the same time are able to deplete this tissue from passenger cells, we will proceed with the transplantation of this tissue into patients with juvenile onset diabetes. In the initial phase of these studies, human fetal pancreatic tissue will be placed beneath the kidney capsule of patients simultaneously receiving a kidney transplant. Our long-term goal is to transplant human fetal pancreatic tissue to non-immunosuppressed patients. The second clincal study is an extension of the previously described clinical parathyroid transplantation. Human parathyroid tissue pretreated and interim hosted will be transplanted to patients with iatrogenic and congenital hypoparathyroidism.