A capsule-based scaffold incorporating decellularized extracellular matrix and curcumin for islet beta cell therapy in type 1 diabetes mellitus.

Autor: Ma H; State Key Laboratory of Fine Chemicals, Dalian R&D Center for Stem Cell and Tissue Engineering, Dalian University of Technology, Dalian 116024, People's Republic of China.; Zhengzhou Institute of Emerging Industrial Technology, Zhengzhou 450000, People's Republic of China., Xu J; State Key Laboratory of Fine Chemicals, Dalian R&D Center for Stem Cell and Tissue Engineering, Dalian University of Technology, Dalian 116024, People's Republic of China.; Zhengzhou Institute of Emerging Industrial Technology, Zhengzhou 450000, People's Republic of China., Fang H; State Key Laboratory of Fine Chemicals, Dalian R&D Center for Stem Cell and Tissue Engineering, Dalian University of Technology, Dalian 116024, People's Republic of China.; Zhengzhou Institute of Emerging Industrial Technology, Zhengzhou 450000, People's Republic of China., Su Y; State Key Laboratory of Fine Chemicals, Dalian R&D Center for Stem Cell and Tissue Engineering, Dalian University of Technology, Dalian 116024, People's Republic of China., Lu Y; State Key Laboratory of Fine Chemicals, Dalian R&D Center for Stem Cell and Tissue Engineering, Dalian University of Technology, Dalian 116024, People's Republic of China.; Zhengzhou Institute of Emerging Industrial Technology, Zhengzhou 450000, People's Republic of China., Shu Y; State Key Laboratory of Fine Chemicals, Dalian R&D Center for Stem Cell and Tissue Engineering, Dalian University of Technology, Dalian 116024, People's Republic of China., Liu W; State Key Laboratory of Fine Chemicals, Dalian R&D Center for Stem Cell and Tissue Engineering, Dalian University of Technology, Dalian 116024, People's Republic of China., Li B; State Key Laboratory of Fine Chemicals, Dalian R&D Center for Stem Cell and Tissue Engineering, Dalian University of Technology, Dalian 116024, People's Republic of China., Cheng YY; Institute for Biomedical Materials and Devices, Faculty of Science, University of Technology, Sydney, NSW 2007, Australia., Nie Y; Zhengzhou Institute of Emerging Industrial Technology, Zhengzhou 450000, People's Republic of China., Zhong Y; Department of Hand and Foot Microsurgery, Dalian Municipal Central Hospital Affiliated of Dalian University of Technology, Dalian 116033, People's Republic of China., Song K; State Key Laboratory of Fine Chemicals, Dalian R&D Center for Stem Cell and Tissue Engineering, Dalian University of Technology, Dalian 116024, People's Republic of China.; Zhengzhou Institute of Emerging Industrial Technology, Zhengzhou 450000, People's Republic of China.
Jazyk: angličtina
Zdroj: Biofabrication [Biofabrication] 2024 Sep 19; Vol. 16 (4). Date of Electronic Publication: 2024 Sep 19.
DOI: 10.1088/1758-5090/ad7907
Abstrakt: The transplantation of islet beta cells offers an alternative to heterotopic islet transplantation for treating type 1 diabetes mellitus (T1DM). However, the use of systemic immunosuppressive drugs in islet transplantation poses significant risks to the body. To address this issue, we constructed an encapsulated hybrid scaffold loaded with islet beta cells. This article focuses on the preparation of the encapsulated structure using 3D printing, which incorporates porcine pancreas decellularized extracellular matrix (dECM) to the core scaffold. The improved decellularization method successfully preserved a substantial proportion of protein (such as Collagen I and Laminins) architecture and glycosaminoglycans in the dECM hydrogel, while effectively removing most of the DNA. The inclusion of dECM enhanced the physical and chemical properties of the scaffold, resulting in a porosity of 83.62% ± 1.09% and a tensile stress of 1.85 ± 0.16 MPa. In teams of biological activity, dECM demonstrated enhanced proliferation, differentiation, and expression of transcription factors such as Ki67, PDX1, and NKX6.1, leading to improved insulin secretion function in MIN-6 pancreatic beta cells. In the glucose-stimulated insulin secretion experiment on day 21, the maximum insulin secretion from the encapsulated structure reached 1.96 ± 0.08 mIU ml -1 , representing a 44% increase compared to the control group. Furthermore, conventional capsule scaffolds leaverage the compatibility of natural biomaterials with macrophages to mitigate immune rejection. Here, incorporating curcumin into the capsule scaffold significantly reduced the secretion of pro-inflammatory cytokine (IL-1 β , IL-6, TNF- α , IFN- γ ) secretion by RAW264.7 macrophages and T cells in T1DM mice. This approach protected pancreatic islet cells against immune cell infiltration mediated by inflammatory factors and prevented insulitis. Overall, the encapsulated scaffold developed in this study shows promise as a natural platform for clinical treatment of T1DM.
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Databáze: MEDLINE