TRANSPLANTATION OF ENDOCRINE TISSUES

拟议研究的目的是开发方法， 胰腺和甲状旁腺组织移植临床成功 而不需要免疫抑制治疗。 建议的研究 这笔赠款的第一部分旨在进一步澄清 通过乘客细胞诱导同种免疫的机制。 我们计划 使用甲状腺移植模型和同类小鼠品系， 与作为临时宿主的遗传上确定的小鼠组合。 我们 将测试我们的假设，即抗原和共刺激分子必须 由一个细胞呈递，以刺激对主要细胞的最大反应。 组织相容性抗原 在拟议研究的第二部分，我们 计划将胎儿胰腺组织移植到糖尿病小鼠体内。 的 临时宿主系统将用于消耗胎鼠胰腺组织 乘客舱里的东西 在高氧环境中培养， 联合免疫毒素治疗过渡宿主。 此外，本发明还提供了一种方法， 碳氟化合物将被用于包裹驻留在胎儿中的乘客细胞。 胰腺组织 所提出的方法的新奇在于 同时使用临时宿主和乘客白细胞清除 治疗方式。 在进一步的实验中， 组织将以类似的方式进行处理， 白细胞含量将通过使用免疫荧光进行测定， 免疫过氧化物酶技术。 如果我们能成功地保护 人胎儿胰腺组织的代谢完整性，同时 能够从乘客细胞中耗尽这个组织，我们将继续进行 将这种组织移植到青少年发病的患者体内， 糖尿病 在这些研究的初始阶段， 同时将组织置于患者的肾包膜下 接受肾脏移植 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 临床研究是先前描述的临床研究的延伸。 甲状旁腺移植 预处理的人甲状旁腺组织， 临时托管将移植给医源性和 先天性甲状旁腺机能减退

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.