Islet cell spheroids produced by a thermally sensitive scaffold: a new diabetes treatment

• Published in: Journal of nanobiotechnology 2024-10, Vol.22 (1), p.657-20, Article 657
• Main Authors: Yao, Xueting, Gong, Zehua, Yin, Wenyan, Li, Hanbing, Douroumis, Dennis, Huang, Lijiang, Li, Huaqiong
• Format: Article
• Language: English
• Subjects: Acrylic Resins - chemistry; Acrylic Resins - pharmacology; Analysis; Animals; Care and treatment; Cellular therapy; Controlled insulin release; Diabetes Mellitus, Experimental; Diabetes Mellitus, Type 1 - therapy; Diagnosis; Glucose - metabolism; Graphite - chemistry; Graphite - pharmacology; Insulin - metabolism; Insulin-Secreting Cells - cytology; Insulin-Secreting Cells - drug effects; Insulin-Secreting Cells - metabolism; Islets of Langerhans - drug effects; Islets of Langerhans - metabolism; Islets of Langerhans Transplantation - methods; Male; Mice; Mice, Inbred C57BL; Microfluidics; Patient outcomes; Porosity; Risk factors; Spheroids, Cellular - drug effects; Spheroids, Cellular - metabolism; Temperature; Thermally sensitive porous scaffold; Thermo-responsiveness; Tissue Scaffolds - chemistry; Type 1 diabetes; Type 1 diabetes mellitus; β-TC-6 cell spheroids
• ISSN: 1477-3155; 1477-3155
• 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.