Joint Research Centre on Medicine, The Affiliated Xiangshan Hospital of Wenzhou Medical University, Ningbo, Zhejiang, 315700, P. R. China.
Zhejiang Engineering Research Center for Tissue Repair Materials, Joint Centre of Translational Medicine, Wenzhou Institute, University of Chinese Academy of Science, Wenzhou, Zhejiang, 325000, P. R. China.
J Nanobiotechnology. 2024 Oct 26;22(1):657. doi: 10.1186/s12951-024-02891-w.
The primary issues in treating type 1 diabetes mellitus (T1DM) through the transplantation of healthy islets or islet β-cells are graft rejection and a lack of available donors. Currently, the majority of approaches use cell encapsulation technology and transplant replacement cells that can release insulin to address transplant rejection and donor shortages. However, existing encapsulation materials merely serve as carriers for islet cell growth. A new treatment approach for T1DM could be developed by creating a smart responsive material that encourages the formation of islet cell spheroids to replicate their 3D connections in vivo and controls the release of insulin aggregates. In this study, we used microfluidics to create thermally sensitive porous scaffolds made of poly(N-isopropyl acrylamide)/graphene oxide (PNIPAM/GO). The material was carefully shrunk under near-infrared light, enriched with mouse insulinoma pancreatic β cells (β-TC-6 cells), encapsulated, and cultivated to form 3D cell spheroids. The controlled contraction of the thermally responsive porous scaffold regulated insulin release from the spheroids, demonstrated using the glucose-stimulated insulin release assay (GSIS), enzyme-linked immunosorbent assay (ELISA), and immunofluorescence assay. Eventually, implantation of the spheroids into C57BL/6 N diabetic mice enhanced the therapeutic effect, potentially offering a novel approach to the management of T1DM.
通过移植健康胰岛或胰岛β细胞来治疗 1 型糖尿病(T1DM)的主要问题是移植物排斥和供体缺乏。目前,大多数方法都使用细胞包封技术和移植可释放胰岛素的替代细胞来解决移植物排斥和供体短缺问题。然而,现有的包封材料仅仅作为胰岛细胞生长的载体。通过创建一种智能响应材料来开发 T1DM 的新治疗方法,该材料可促进胰岛细胞球体的形成,以复制其在体内的 3D 连接,并控制胰岛素聚集体的释放。在这项研究中,我们使用微流控技术创建了由聚(N-异丙基丙烯酰胺)/氧化石墨烯(PNIPAM/GO)制成的热敏感多孔支架。该材料在近红外光下被仔细收缩,富集了小鼠胰岛素瘤胰岛β细胞(β-TC-6 细胞),然后进行包封并培养以形成 3D 细胞球体。通过葡萄糖刺激胰岛素释放测定(GSIS)、酶联免疫吸附测定(ELISA)和免疫荧光测定来证实热响应多孔支架的受控收缩调节了球体中胰岛素的释放。最终,将球体植入 C57BL/6N 糖尿病小鼠中增强了治疗效果,为 T1DM 的管理提供了一种新方法。