Survival of human islets in microbeads containing high guluronic acid alginate crosslinked with Ca2+ and Ba2+.

Survival of human islets in microbeads containing high guluronic acid alginate crosslinked with Ca2+ and Ba2+.
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DOI:
10.1111/xen.12009
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发表时间:
2012-11
影响因子:
3.9
通讯作者:
Strand BL
Strand BL
中科院分区:
医学3区
文献类型:
--
作者:
Qi M;Mørch Y;Lacík I;Formo K;Marchese E;Wang Y;Danielson KK;Kinzer K;Wang S;Barbaro B;Kolláriková G;Chorvát D Jr;Hunkeler D;Skjåk-Braek G;Oberholzer J;Strand BL

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广泛使用胰岛移植治疗1型糖尿病的主要障碍仍然是合适供体数量不足和需要免疫抑制。微囊化已被提出作为保护移植胰岛免受宿主免疫系统影响的手段。本研究探讨了钙/钡海藻酸钠微球包裹的人胰岛移植到糖尿病Balb/c小鼠体内的功能。所有移植了3,000个胰岛当量(IEQ)的包封人胰岛的小鼠(n = 29)在移植后1天达到正常血糖,并在延长的时间段内保持正常血糖(平均移植物存活134 ± 17天)。相比之下,移植等量未包封的人类胰岛的糖尿病Balb/c小鼠在移植后2 - 7天内出现胰岛排斥(n = 5)。在232天后回收的微珠(n = 3)被发现几乎没有纤维化过度生长,并且含有活的胰岛素阳性胰岛。对回收的微珠的免疫荧光染色显示F4/80阳性巨噬细胞和α SMA阳性成纤维细胞,但没有CD3阳性T淋巴细胞。钙/钡海藻酸钠微球在无免疫抑制的免疫活性小鼠体内能保护人胰岛免受异种排斥反应。然而,移植物最终失败,可能继发于巨噬细胞介导的异物反应。
The main hurdles to the wide spread use of islet transplantation for the treatment of type 1 diabetes continue to be the insufficient number of appropriate donors and the need for immunosuppression. Microencapsulation has been proposed as a means to protect transplanted islets from the host’s immune system. The present study investigated the function of human pancreatic islets encapsulated in Ca2+/Ba2+-alginate microbeads intraperitoneally transplanted in diabetic Balb/c mice. All mice transplanted with encapsulated human islets (n=29), at a quantity of 3,000 islet equivalent (IEQ), achieved normoglycemia one day after transplantation and retained normoglycemia for extended periods of time (mean graft survival 134 ± 17 days). In comparison, diabetic Balb/c mice transplanted with an equal amount of non-encapsulated human islets rejected the islets within 2–7 days after transplantation (n=5). Microbeads retrieved after 232 days (n=3) were found with little to no fibrotic overgrowth and contained viable insulin positive islets. Immunofluorescent staining on the retrieved microbeads showed F4/80 positive macrophages and alpha SMA positive fibroblasts but no CD3 positive T lymphocytes. The Ca2+/Ba2+-alginate microbeads can protect human islets from xenogeneic rejection in immunocompetent mice without immunosuppression. However, grafts ultimately failed likely secondary to a macrophage mediated foreign body reaction.
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