Biosensors for Bioengineering, Institute for Bioengineering of Catalonia (IBEC), The Barcelona Institute of Science and Technology (BIST), Baldiri I Reixac, 10-12, Barcelona 08028, Spain.
ICREA-Institució Catalana de Recerca i Estudis Avançats, 08010 Barcelona, Spain.
Biofabrication. 2021 May 28;13(3). doi: 10.1088/1758-5090/ac00c3.
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-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-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-cells, representing a suitable technique to generate-cell clusters to study pancreatic islet function.
用于 2 型糖尿病（T2D）研究的胰岛通常受到功能性胰岛模型的可用性限制。为了克服从不同来源（如动物模型或人类供体）获得胰岛的局限性，永生化细胞系作为产生胰岛素的 INS1E 细胞已成为模拟胰岛素相关疾病的有效替代方法。然而，永生化细胞系主要用于平面或单层分布，而不像胰岛那样具有球体样结构。为了生成胰岛样结构，使用支架作为促进细胞聚集的有效工具。传统的水凝胶包封方法不能满足胰腺组织工程的所有要求，因为其较差的营养和氧气扩散会导致细胞死亡。在这里，我们使用冷冻凝胶化技术来开发一种更具机械和物理特性的支架，以用于胰腺组织工程。本研究表明，与基于明胶的支架相比，羧甲基纤维素（CMC）冷冻凝胶促使细胞形成细胞簇，而后者不会诱导这种细胞组织。此外，CMC 冷冻凝胶实现的高孔隙率允许我们创建特定范围的拟胰岛。在 CMC 支架内形成的拟胰岛在长达 7 天的时间内保持细胞活力，并且对葡萄糖的反应优于传统的单层培养。总体而言，我们的结果表明 CMC 支架可用于控制产生胰岛素的细胞的组织和功能，这是一种用于生成细胞簇以研究胰岛功能的合适技术。
