Lee J I, Kim H W, Kim J Y, Bae S J, Joo D J, Huh K H, Fang Y H, Jeong J H, Kim M S, Kim Y S
Department of Biomedical Science and Technology, Regenerative Medicine Laboratory, Konkuk University, Seoul, South Korea.
Transplant Proc. 2012 May;44(4):1091-4. doi: 10.1016/j.transproceed.2012.02.015.
Improving human islet transplantation is often limited by the shortage of donors and the side effects of immunosuppressive agents. If immunoisolation is properly used, it can overcome these obstacles. Because artificial materials are adopted in this technique, however, there are still multiple issues with biocompatibility and foreign body reactions. We developed a chondrocyte microencapsulated immunoisolated islet (CMI-islet) that allows living cells to act as the immunoisolating material. To manufacture CMI-islets for xenotransplantation, isolated rat pancreatic islets were placed on low cell-binding culture dishes. Subsequently, expanded canine auricular cartiage primary cells were seeded on these dishes at a high density and maintained in a suspended state via a shaking culture system. Morphological evaluations showed good islet viability and a clear progression of the islet- encapsulation events. When the cells were challenged with glucose, they were able to secrete sufficient insulin according to glucose concentrations. The CMI-islets responded better to the glucose challenge than did nude pancreatic islets and created better glucose-insulin feedback regulation. Moreover, insulin secretion into the culture medium was confirmed over a period of 100 days, showing the survival and secretory capacity of the CMI-islet cells. By microencapsulating pancreatic islets with recipient ear cartilage cells, long-term insulin secretion can be maintained and the response to glucose challenges improved. This new immunodelusion technology differs from other immunoisolation techniques in that the donor tissue is enclosed with the recipient's tissue, thus allowing the transplanted cells to be recognized as recipient cells. This microencapsulation method may lead to developing viable xenotransplantation techniques that do not use immunosuppressive drugs.
人类胰岛移植的改善常常受到供体短缺和免疫抑制剂副作用的限制。如果能正确使用免疫隔离技术，就可以克服这些障碍。然而，由于该技术采用了人工材料，在生物相容性和异物反应方面仍然存在多个问题。我们开发了一种软骨细胞微囊化免疫隔离胰岛（CMI-胰岛），它使活细胞能够作为免疫隔离材料。为了制造用于异种移植的CMI-胰岛，将分离的大鼠胰岛置于低细胞结合培养皿上。随后，将扩增的犬耳软骨原代细胞以高密度接种在这些培养皿上，并通过振荡培养系统维持在悬浮状态。形态学评估显示胰岛活力良好，胰岛包封过程进展清晰。当细胞受到葡萄糖刺激时，它们能够根据葡萄糖浓度分泌足够的胰岛素。CMI-胰岛对葡萄糖刺激的反应比裸胰腺胰岛更好，并产生了更好的葡萄糖-胰岛素反馈调节。此外，在100天的时间里证实了胰岛素分泌到培养基中，表明CMI-胰岛细胞的存活和分泌能力。通过用受体耳软骨细胞对胰腺胰岛进行微囊化，可以维持长期胰岛素分泌并改善对葡萄糖刺激的反应。这种新的免疫隔离技术与其他免疫隔离技术的不同之处在于，供体组织被受体组织包裹，从而使移植的细胞被识别为受体细胞。这种微囊化方法可能会导致开发出不使用免疫抑制药物的可行异种移植技术。
