Improving cellular function and immune protection via layer-by-layer nanocoating of pancreatic islet β-cell spheroids cocultured with mesenchymal stem cells

Islet transplantation as a therapy for type 1 diabetes is currently limited by lack of primary transplant material from human donors and post‐transplantation loss of islets caused by adverse immune and nonimmune reactions. This study aimed to develop a novel strategy to create microenvironment for i...

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Published in:Journal of biomedical materials research. Part A 2012-06, Vol.100A (6), p.1628-1636
Main Authors: Bhaiji, Tasneem, Zhi, Zheng-Liang, Pickup, John C.
Format: Article
Language:English
Subjects:
Animals
Biological and medical sciences
Cell Line
Cell Survival
Cells, Cultured
Coculture Techniques - methods
Cytokines - immunology
diabetes mellitus
Diabetes. Impaired glucose tolerance
Endocrine pancreas. Apud cells (diseases)
Endocrinopathies
Etiopathogenesis. Screening. Investigations. Target tissue resistance
Heparin - chemistry
Humans
immunoprotection
insulin
Insulin - metabolism
Insulin-Secreting Cells - cytology
Insulin-Secreting Cells - immunology
Insulin-Secreting Cells - metabolism
Islets of Langerhans Transplantation - methods
Medical sciences
mesenchymal stem cells
Mesenchymal Stromal Cells - cytology
Mesenchymal Stromal Cells - immunology
Mesenchymal Stromal Cells - metabolism
Mice
Mice, Inbred C57BL
MIN6 β-cells
nanoencapsulation
Nanostructures - chemistry
Phosphorylcholine - chemistry
Polylysine - chemistry
Spheroids, Cellular - cytology
Spheroids, Cellular - immunology
Spheroids, Cellular - metabolism
Surgery (general aspects). Transplantations, organ and tissue grafts. Graft diseases
Technology. Biomaterials. Equipments
Tissue Scaffolds - chemistry
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Summary:Islet transplantation as a therapy for type 1 diabetes is currently limited by lack of primary transplant material from human donors and post‐transplantation loss of islets caused by adverse immune and nonimmune reactions. This study aimed to develop a novel strategy to create microenvironment for islets via integration of nanoencapsulation with cell cocultures, thereby enhancing their survival and function. The nanoencapsulation was achieved via layer‐by‐layer deposition of phosphorycholine‐modified poly‐L‐lysine/heparin leading to the formation of nanometer‐thick multilayer coating on islets. Spheroids formed by coculturing MIN6 β‐cells with mesenchymal stem cells in suspension were used as the tool for testing encapsulation. Coculturing MSCs with MIN6 cells allowed the cell constructs to enhance structural and morphologic stability with improved insulin secretory function and render them less susceptible to inflammatory cytokine‐induced apoptosis. Combining nanoencapsulation with coculture of MSCs/MIN6 resulted in higher glucose responsiveness, and lower antibody binding and apoptosis‐inducing effects of cytokines. This strategy of nanoencapsulating islet cocultures appears promising to improve cellular delivery of insulin for treating type 1 diabetes. © 2012 Wiley Periodicals, Inc. J Biomed Mater Res Part A, 2012.
ISSN:1549-3296
1552-4965
DOI:10.1002/jbm.a.34111