title: Improving cellular function and immune protection via layer-by-layer nanocoating of pancreatic islet β-cell spheroids cocultured with mesenchymal stem cells.
abstract: 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.
authors.affiliation: Diabetes Research Group, King's College London School of Medicine, Guy's Hospital, London SE1 1UL, United Kingdom.
authors.forename: Tasneem
authors.initials: T
authors.lastname: Bhaiji
authors.forename: Zheng-Liang
authors.initials: ZL
authors.lastname: Zhi
authors.forename: John C
authors.initials: JC
authors.lastname: Pickup
mesh_terms: D000818:Animals; D002460:Cell Line; D002470:Cell Survival; D002478:Cells, Cultured; D018920:Coculture Techniques / Q000379:methods*; D016207:Cytokines / Q000276:immunology; D006493:Heparin / Q000737:chemistry; D006801:Humans; D007328:Insulin / Q000378:metabolism; D050417:Insulin-Secreting Cells / Q000166:cytology* / Q000276:immunology / Q000378:metabolism; D016381:Islets of Langerhans Transplantation / Q000379:methods; D059630:Mesenchymal Stem Cells / Q000166:cytology* / Q000276:immunology / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D049329:Nanostructures / Q000737:chemistry; D010767:Phosphorylcholine / Q000737:chemistry; D011107:Polylysine / Q000737:chemistry; D018874:Spheroids, Cellular / Q000166:cytology / Q000276:immunology / Q000378:metabolism; D054457:Tissue Scaffolds / Q000737:chemistry*
chemical_list: D016207:Cytokines; D007328:Insulin; D010767:Phosphorylcholine; D011107:Polylysine; D006493:Heparin