Department of Biomedical Engineering, College of Health Science, Korea University, Jeongneung-dong, Seongbuk-gu, Seoul 136-703, Republic of Korea.
Biomaterials. 2013 Nov;34(33):8122-30. doi: 10.1016/j.biomaterials.2013.07.079. Epub 2013 Aug 5.
Pancreatic islet transplantation is a promising method for treatment of type 1 diabetes mellitus. However, transplanted islets can be destroyed due to host immune reactions. To immunologically protect transplanted islets, here an immunoprotective microfiber including islets by using a polydimethylsiloxane (PDMS)-based microfluidic device is newly designed. A cylindrical-flow channel in the microfluidic platform is used for producing collagen-alginate composite (CAC) fibers. This enables mass production and uniform diameter distribution (<250 μm) without protruding islets. Collagen, which is the main extracellular matrix component, is added to alginate to mimic the native islet microenvironment. Compared to free islets (control) and alginate-fiber-encapsulated islets, CAC-fiber-encapsulated islets show higher viability and normal insulin secretion. When CAC-fiber-encapsulated islets (1200 islet equivalent) are implanted into the intraperitoneal cavity of streptozotocin-induced diabetic BALB/C mice, the blood glucose levels of all mice return to normoglycemia. Moreover, intraperitoneal glucose tolerance tests demonstrate that islets in the CAC-fiber have similar glucose responsiveness to those of non-diabetic normal mice. These results are attributed to the immunoprotection of the transplanted islets from host immune reactions. On the other hand, all free islets are completely rejected within a week due to severe immune responses. Collectively, fabrication of CAC fibers using microfluidic devices can be used for successful islet transplantation.
胰岛移植是治疗 1 型糖尿病的一种很有前途的方法。然而，移植的胰岛可能会被宿主的免疫反应破坏。为了对移植的胰岛进行免疫保护，本研究新设计了一种包含胰岛的免疫保护微纤维，该纤维使用了一种基于聚二甲基硅氧烷（PDMS）的微流控装置。微流控平台中的圆柱形流道用于生产胶原-藻酸盐复合（CAC）纤维。这使得可以进行大规模生产和均匀的直径分布（<250μm），而不会突出胰岛。胶原是主要的细胞外基质成分，被添加到藻酸盐中以模拟天然胰岛微环境。与游离胰岛（对照）和藻酸盐纤维包封的胰岛相比，CAC 纤维包封的胰岛显示出更高的活力和正常的胰岛素分泌。当将 CAC 纤维包封的胰岛（1200 胰岛当量）植入链脲佐菌素诱导的糖尿病 BALB/C 小鼠的腹腔内时，所有小鼠的血糖水平均恢复正常。此外，腹腔内葡萄糖耐量试验表明，CAC 纤维中的胰岛对葡萄糖的反应与非糖尿病正常小鼠相似。这些结果归因于移植胰岛免受宿主免疫反应的免疫保护。另一方面，由于严重的免疫反应，所有游离的胰岛在一周内都被完全排斥。总之，使用微流控装置制造 CAC 纤维可用于成功的胰岛移植。
