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.

Nanoencapsulation of Human Adipose Mesenchymal Stem Cells: Experimental Factors Role to Successfully Preserve Viability and Functionality of Cells

“…[24], multilayer nanoencapsulation described by Bahiji et al [25] and the protection against physical stress by layer-by layer cell coating described by Matsuzawa et al [26], we have described the first successfully single cell nanoencapsulation of human adipose derived mesenchymal stem cells identifying an appropriate combination of polyelectrolytes that keep cell viability and functionality of the MSC for long-term cellular therapy application.…”

Morphological characteristics and identification of islet‐like cells derived from rat adipose‐derived stem cells cocultured with pancreas adult stem cells

“…For example, it has been shown that BMSCs incubated with a solution from the regenerating pancreas of the rat differentiate into insulin-producing islet-like cells (Choi et al, 2005). Similarly, coculture of pancreatic b-cells with mesenchymal stem cells using layer-by-layer nanocoating, enhanced the structural and morphologic stability of b-cells, improved insulin secretion, and rendered them less susceptible to inflammatory cytokine-induced apoptosis (Bhaiji et al, 2012). Furthermore, coculture of hBMSCs with retinal pigment epithelial cells using a transwell approach has previously been shown to induce differentiation of the stem cells into functional retinal pigment epithelial cells (Duan et al, 2013).…”

Minireview: Directed Differentiation and Encapsulation of Islet β-Cells—Recent Advances and Future Considerations

“…The assembly of polymers based on sequential adsorption of oppositely charged components is a universal surface modification approach that will produce coatings with controlled thickness, permeability, mechanical properties and surface chemistry. The biocompatible multilayer coatings are capable of regulating molecular permeability and display immunoprotection; however, despite the potential of the LbL strategy for islet modification, the main drawback of the approach is cytotoxicity of poly(L-lysine) and poly(ethylene imine) cationic compounds used in assembly (119,120). Cytotoxicity can be reduced by varying polycation concentration, exposure time, and introducing PEG grafts, but polycation-based systems are still challenging for cell modification (104,118).…”