Size effect of engineered islets prepared using microfabricated wells on islet cell function and arrangement.
Size effect of engineered islets prepared using microfabricated wells on islet cell function and arrangement.
复制标题
使用微生物井在胰岛细胞功能和排列上制备的工程胰岛的尺寸影响。
DOI：
10.1016/j.heliyon.2016.e00129
复制
发表时间：
2016-06
期刊：
影响因子：
4
通讯作者：
Uchigata Y
中科院分区：
文献类型：
--
作者：
Ichihara Y;Utoh R;Yamada M;Shimizu T;Uchigata Y
胰岛是由α和β细胞组成的异质性簇，直径从50微米到几百微米不等。与大胰岛相比，天然小胰岛在体外具有更高的胰岛素分泌能力，并提供更好的移植结果。在这项研究中，我们使用精确制造的不同直径(100、300或500μm)的琼脂糖凝胶微孔，从分散的大鼠胰岛细胞制备微工程假性胰岛，以研究大小可控的胰岛细胞聚集体的功能和存活。我们观察到，用100∼m微孔制备的平均直径为60μm的小假性胰岛中几乎没有死亡细胞。相反，我们观察到使用300和500μm微孔制备的较大的假性胰岛中有更多的死亡细胞。在较小的假性胰岛中，低氧细胞的相对数量显着较低，而在较大的假性胰岛的核心区存在低氧条件。此外，我们还发现，小尺寸的假性胰岛重建了α和β细胞在体内的组织样排列，并恢复了对高糖反应的高胰岛素分泌能力。这些结果清楚地表明，精确控制假性胰岛的大小对于维持胰岛细胞的功能和体外存活是必不可少的。小尺寸假性胰岛可能为通过胰岛重组和移植治疗1型糖尿病提供了一种更好的治疗途径。
Pancreatic islets are heterogeneous clusters mainly composed of α and β cells, and these clusters range in diameter from 50 to several hundred micrometers. Native small islets are known to have a higher insulin secretion ability in vitro and to provide better transplantation outcomes when compared with large islets. In this study, we prepared microengineered pseudo-islets from dispersed rat islet cells using precisely-fabricated agarose gel-based microwells with different diameters (100, 300, or 500 μm) to investigate the function and survival of islet cell aggregates with well-controlled sizes. We observed that dead cells were rarely present in the small pseudo-islets with an average diameter of ∼60 μm prepared using 100 μm microwells. In contrast, we observed more dead cells in the larger pseudo-islets prepared using 300 and 500 μm microwells. The relative amount of hypoxic cells was significantly low in the small pseudo-islets whereas a hypoxic condition was present in the core region of the larger pseudo-islets. In addition, we found that the small-sized pseudo-islets reconstituted the in vivo-tissue like arrangement of the α and β cells, and restored the high insulin secretory capacity in response to high glucose. These results clearly suggest that precise size control of pseudo-islets is essential for maintaining islet cell function and survival in vitro. The small-sized pseudo-islets may be advantageous for providing a better therapeutic approach for treating type 1 diabetes mellitus via islet reorganization and transplantation.