Micro/nanoscale technologies for the development of hormone-expressing islet-like cell clusters

Micro/nanoscale technologies for the development of hormone-expressing islet-like cell clusters
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DOI:
10.1007/s10544-012-9657-4
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发表时间:
2012-08-01
影响因子:
2.8
通讯作者:
Gooch, Keith J.
Gooch, Keith J.
中科院分区:
工程技术3区
文献类型:
--
作者:
Gallego-Perez, Daniel;Higuita-Castro, Natalia;Gooch, Keith J.

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Insulin-expressing islet-like cell clusters derived from precursor cells have significant potential in the treatment of type-I diabetes. Given that cluster size and uniformity are known to influence islet cell behavior, the ability to effectively control these parameters could find applications in the development of anti-diabetic therapies. In this work, we combined micro and nanofabrication techniques to build a biodegradable platform capable of supporting the formation of islet-like structures from pancreatic precursors. Soft lithography and electrospinning were used to create arrays of microwells (150-500 mu m diameter) structurally interfaced with a porous sheet of micro/nanoscale polyblend fibers (similar to 0.5-10 mu m in cross-sectional size), upon which human pancreatic ductal epithelial cells anchored and assembled into insulin-expressing 3D clusters. The microwells effectively regulated the spatial distribution of the cells on the platform, as well as cluster size, shape and homogeneity. Average cluster cross-sectional area (similar to 14000-17500 mu m(2)) varied in proportion to the microwell dimensions, and mean circularity values remained above 0.7 for all microwell sizes. In comparison, clustering on control surfaces (fibers without microwells or tissue culture plastic) resulted in irregularly shaped/sized cell aggregates. Immunoreactivity for insulin, C-peptide and glucagon was detected on both the platform and control surfaces; however, intracellular levels of C-peptide/cell were similar to 60 % higher on the platform.