Qi Meirigeng, Strand Berit Løkensgard, Mørch Yrr, Lacík Igor, Wang Yong, Salehi Payam, Barbaro Barbara, Gangemi Antonio, Kuechle Joseph, Romagnoli Travis, Hansen Michael A, Rodriguez Lisette A, Benedetti Enrico, Hunkeler David, Skjåk-Braek Gudmund, Oberholzer José
Department of Surgery, University of Illinois at Chicago, Illinois, USA.
Artif Cells Blood Substit Immobil Biotechnol. 2008;36(5):403-20. doi: 10.1080/10731190802369755.
Microencapsulation may allow for immunosuppression-free islet transplantation. Herein we investigated whether human islets can be shipped safely to a remote encapsulation core facility and maintain in vitro and in vivo functionality. In non-encapsulated islets before and encapsulated islets after shipment, viability was 88.3+/-2.5 and 87.5+/-2.7% (n=6, p=0.30). Stimulation index after static glucose incubation was 5.4+/-0.5 and 6.3+/-0.4 (n=6, p=0.18), respectively. After intraperitoneal transplantation, long-term normoglycemia was consistently achieved with 3,000, 5,000, and 10,000 IEQ encapsulated human islets. When transplanting 1,000 IEQ, mice returned to hyperglycemia after 30-55 (n=4/7) and 160 days (n=3/7). Transplanted mice showed human oral glucose tolerance with lower glucose levels than non-diabetic control mice. Capsules retrieved after transplantation were intact, with only minimal overgrowth. This study shows that human islets maintained the viability and in vitro function after encapsulation and the inhomogeneous alginate-Ca(2+)/Ba(2+) microbeads allow for long-term in vivo human islet graft function, despite long-distance shipment.
微囊化可能允许进行无免疫抑制的胰岛移植。在此,我们研究了人胰岛是否能够安全运输至远程微囊化核心设施,并维持其体外和体内功能。在运输前的未微囊化胰岛和运输后的微囊化胰岛中,存活率分别为88.3±2.5%和87.5±2.7%(n = 6,p = 0.30)。静态葡萄糖孵育后的刺激指数分别为5.4±0.5和6.3±0.4(n = 6,p = 0.18)。腹腔内移植后,3000、5000和10000胰岛当量的微囊化人胰岛持续实现了长期正常血糖。移植1000胰岛当量时,小鼠在30 - 55天(n = 4/7)和160天后(n = 3/7)恢复高血糖。移植的小鼠表现出人体口服葡萄糖耐量,血糖水平低于非糖尿病对照小鼠。移植后回收的胶囊完整,仅有轻微的过度生长。这项研究表明,人胰岛在微囊化后维持了活力和体外功能,并且尽管经过长途运输,不均匀的藻酸盐 - 钙(2 +)/钡(2 +)微珠仍能实现人胰岛移植的长期体内功能。