Long-term in vitro human pancreatic islet culture using three-dimensional microfabricated scaffolds

作者：Daoud Jamal T; Petropavlovskaia Maria S; Patapas Jason M; Degrandpre Christian E; DiRaddo Robert W; Rosenberg Lawrence; Tabrizian Maryam^*

来源：Biomaterials, 2011, 32(6): 1536-1542.

DOI：10.1016/j.biomaterials.2010.10.036

• ECM(extracellular matrix)
• Microfabricated biodegradable scaffold
• Long-term culture of human islets
• Islet functionality

Human pancreatic islet in vitro culture is very challenging and requires the presence of various extra cellular matrix (ECM) components in a three-dimensional environment, which provides mechanical and biological support. The development of such an environment is vital in providing favourable conditions to preserve human islets in long-term culture. In this study, we investigated the effects of human islet culture within various three-dimensional environments; collagen I gel, collagen I gel supplemented with ECM components fibronectin and collagen IV, and microfabricated scaffold with ECM-supplemented gel. The cultured human islets were analyzed for functionality, gene expression and hormone content following long-term in vitro culture. It was clear the incorporation of ECM components within the three-dimensional support improved prolonged culture. However, long-term and highly uniform human islet culture within a microfabricated scaffold, with controlled pore structures, coupled with the presence of ECM components, displayed an insulin release profile similar to freshly isolated islets, yielding a stimulation index of similar to 1.8. Moreover, gene expression was markedly increased for all pancreatic genes, giving a similar to 50-fold elevation of insulin gene expression with respect to suspension culture. The distribution and presence of pancreatic hormones was also highly elevated. These findings provide a platform for the long-term maintenance and preservation of human pancreatic islets in vitro.

• 出版日期2011-2