Collagen matrix support of pancreatic islet survival and function

Abstract

Diabetes mellitus is a chronic condition resulting from insufficient β-cell mass, which leads to improper glycemia regulation. Research efforts have focused on expanding islets and β-cells in vitro for use in cell-based therapies to cure diabetes. Collagens are triple-helix extracellular matrix proteins with widespread expression in mammals. With multiple functions, collagen can provide structural integrity in addition to mediating cellular signaling. In the pancreas, collagens I and IV are abundant and support cell structures while also stimulating cell surface receptors to influence pancreatic cell processes. Collagen-based materials and scaffolds have also been used to assist in the maintenance and expansion of islet cells in vitro, primarily through integrin and discoindin domain receptors. Islet transplantation using collagen-based scaffolds may improve long-term glycemic control, but progressive research efforts are required to realize this potential in humans. This review will outline the critical role played by native collagens I and IV and their receptors in maintaining islet function. The advantages of using collagens I and IV as culture gels/scaffolds and islet encapsulation vehicles for transplantation will be described.

Real architecture For 3D Tissue (RAFT™) culture system improves viability and maintains insulin and glucagon production of mouse pancreatic islet cells

“…Dissected islets require the re-establishment of cell–matrix interactions in order to preserve hormone secretion and viability (Wang and Rosenberg 1999). Collagen, as an ECM component in connective tissues can support spheroid integrity and modulate cell signalling e. g. via collagen-integrin interactions (Riopel and Wang 2014). Encapsulation of rat embryonic pancreas precursors in collagen type I matrix incorporated in polyethylene glycol hydrogel (PEG) supported precursor cell development (Mason et al 2009).…”

Biocompatible Scaffolds: An Effective Means for Improving Islet Cells Viability and Function

“…Further, Yep, et al showed that collagen IV-modified scaffolds could promote islet cell viability, decreased early-stage islet cell apoptosis, improved islet metabolic function and insulin release, and eventually restored euglycemia significantly faster [39]. The role of collagen based ECMs in support of islet viability and function was reviewed by Riopel and Wang and they concluded that embedding islets within a mixture of native ECM components that are commonly found in the pancreas is required to preserve islet cell survival and function [12]. In a separate strategy, synthetic peptide sequences have been identified and synthesized to imitate the effect of ECM proteins in stimulating the integrin receptors.…”

“…These collagens play an important role in supporting pancreatic islets. Fibronectins and laminins are also important components of islet ECM [12]. Fibronectins and laminins mainly connect cells to the underlying matrix and play key roles in cell adhesion and signalling.…”

“…Although in the first year post-transplantation basement membrane and Extracellular Matrix (ECM) surrounding the islets. These components are essential for islet integrity and damage to the islet native ECM triggers functional impairment of islets and eventual islet cell apoptosis [12][13][14]. In this view, reestablishment of the interactions between islet cells and the elements of their local microenvironment may preserve islet cell viability and function and eventually lead to improvement of the outcome of islet cells replacement therapies.…”

Encapsulation technologies in beta cell replacement therapies for Type 1 diabetes

“…Several novel strategies to ameliorate hypoxia in encapsulated cells including the use of oxygen-generating chemicals [polydimethylsiloxane (PDMS)--encapsulated solid calcium peroxide] [151], co-encapsulation with photosynthetically-active microorganisms (Synechococcus lividus) [152] and implantable devices fitted with access ports to enable direct O2 delivery -the β-Air device [153] -are all being evaluated.…”