Islet Cell Transplantation: In Vivo and in Vitro Functional Assessment of Nonhuman Primate Pancreatic Islets
Islet Cell Transplantation: In Vivo and in Vitro Functional Assessment of Nonhuman Primate Pancreatic Islets
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DOI：
10.1177/096368970000900311
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发表时间：
2000-05
影响因子：
3.3
通讯作者：
Alessandra Rammcoli;N. Cautero;C. Ricordi;M. Masetti;R. Molano;L. Inverardi;R. Alejandro;N. Kenyon
中科院分区：
文献类型：
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作者：
Alessandra Rammcoli;N. Cautero;C. Ricordi;M. Masetti;R. Molano;L. Inverardi;R. Alejandro;N. Kenyon
作为治疗I型糖尿病的一种治疗方法，朗格汉斯胰岛移植提供了皮下注射胰岛素的另一种选择。通过移植胰岛使血糖水平正常化可能会预防糖尿病相关并发症的发生。在将胰岛细胞移植到肝脏后，需要解决与排斥反应、自身免疫复发和局部炎症相关的问题，然后才能将胰岛细胞移植视为在大量患者中进行的正当程序。胰岛细胞分离在小动物身上已经相当成功，但将这种方法移植到非人类灵长类动物身上就没有那么有意义了。在非人灵长类动物模型中遇到的主要问题之一是难以分离出足够数量的功能性胰岛用于移植。本研究的目的是开发一种方法，从非人类灵长类动物中分离出足够数量的存活胰岛，以便逆转糖尿病。通过对自动化的人胰岛分离方法进行微小的修改，我们能够在体外获得对葡萄糖刺激正常反应的有活力的、有功能的胰岛。这些胰岛也能够逆转免疫受损的裸鼠的糖尿病，这些裸鼠因链脲佐菌素而患上糖尿病。这种胰岛细胞分离方法使我们能够在临床前的非人类灵长类动物模型中进行同种异体胰岛细胞移植的方案。
Transplantation of pancreatic islets of Langerhans as a therapeutic approach for treatment of type I diabetes offers an alternative to subcutaneous insulin injections. Normalization of blood glucose levels by transplanted islets may prevent the development of diabetes-related complications. Problems related to rejection, recurrence of autoimmunity, and local inflammation upon transplantation of islets into the liver need to be solved before the implementation of islet cell transplantation can be viewed as a justifiable procedure in a large cohort of patients. Islet cell isolation has been quite successful in small animals, but the translation of this approach to nonhuman primates has been less rewarding. One of the main problems encountered in nonhuman primate models is the difficulty of isolating an adequate number of functional islets for transplantation. The aim of the present study was to develop a method for isolating a sufficient number of viable islets from nonhuman primates to allow for reversal of diabetes. By implementing minor modifications in the automated method for human islet isolation we were able to obtain viable, functional islets that responded normally to glucose stimulation in vitro. These islets were also able to reverse diabetes in immunocompromised nude mice, rendered diabetic by streptozotocin. This method of islet cell isolation has enabled us to proceed with protocols of allogeneic islet cell transplantation in preclinical, nonhuman primate models.