Abstract
In vitro research for the study of type 2 diabetes (T2D) is frequently limited by the availability of a functional model for islets of Langerhans. To overcome the limitations of obtaining pancreatic islets from different sources, such as animal models or human donors, immortalized cell lines as the insulin-producing INS1E β-cells have appeared as a valid alternative to model insulin-related diseases. However, immortalized cell lines are mainly used in flat surfaces or monolayer distributions, not resembling the spheroid-like architecture of the pancreatic islets. To generate islet-like structures, the use of scaffolds appeared as a valid tool to promote cell aggregations. Traditionally-used hydrogel encapsulation methods do not accomplish all the requisites for pancreatic tissue engineering, as its poor nutrient and oxygen diffusion induces cell death. Here, we use cryogelation technology to develop a more resemblance scaffold with the mechanical and physical properties needed to engineer pancreatic tissue. This study shows that carboxymethyl cellulose (CMC) cryogels prompted cells to generate β-cell clusters in comparison to gelatin-based scaffolds, that did not induce this cell organization. Moreover, the high porosity achieved with CMC cryogels allowed us to create specific range pseudoislets. Pseudoislets formed within CMC-scaffolds showed cell viability for up to 7 d and a better response to glucose over conventional monolayer cultures. Overall, our results demonstrate that CMC-scaffolds can be used to control the organization and function of insulin-producing β-cells, representing a suitable technique to generate β-cell clusters to study pancreatic islet function.
Highlights
The worldwide prevalence of type 2 diabetes (T2D) has been increasing over the last decades, attaining the status of a global pandemic [1]
We show that INS1E pseudoislets ameliorated their response to glucose stimuli and presented a more closely related mature β-cell phenotype than nonorganized cells seeded in gelatin-based cryogels or a traditional well-plate
We found that after 7 d of culture, encapsulated cells retained their viability compared to non-encapsulated cells, and both gelatin and carboxymethyl cellulose (CMC) scaffolds presented a similar percentage of viability (figures 4(a) and (b))
Summary
The worldwide prevalence of type 2 diabetes (T2D) has been increasing over the last decades, attaining the status of a global pandemic [1]. T2D is a chronic metabolic disorder characterized by hyperglycemia. It usually occurs when the peripheral tissues cannot effectively use the insulin that pancreas produces. This situation leads to an increased insulin demand and the insulin-producing β-cells respond by activating compensatory pathways to improve their secretory capacity. Cell lines are a suitable alternative to model T2D in vitro and avoid human donor material or primary mouse pancreatic islets. Both mouse insulinoma MIN6 and rat insulinoma INS1E cell lines are commonly used for in vitro research. INS1E cells have been reported to present better responsiveness to glucose within the physiological range and relatively high insulin content [2, 3]
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