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Fucoidan Hydrogels Significantly Alleviate Oxidative Stress and Enhance the Endocrine Function of Encapsulated Beta Cells
Authors:Lara L Reys  Vijayaganapathy Vaithilingam  Mireille M J P E Sthijns  Eduardo Soares  Timo Rademakers  Rick de Vries  Sami G Mohammed  Denise de Bont  Marlon J Jetten  Carolin Hermanns  Omar Paulino da Silva Filho  Adam Stell  Nizar I Mourad  Pierre Gianello  Vanessa L S LaPointe  Simone S Silva  Rui L Reis  Tiago H Silva  Aart A van Apeldoorn
Affiliation:1. 3B's Research Group, I3Bs – Research Institute on Biomaterials, Biodegradables and Biomimetics of University of Minho, Headquarters of the European Institute of Excellence on Tissue Engineering and Regenerative Medicine, AvePark, Barco, Guimarães, 4805-017 Portugal;2. Cell Biology Inspired Tissue Engineering (CBITE), MERLN Institute for Technology-Inspired Regenerative Medicine, Maastricht University, Universiteitssingel 40, ER, Maastricht, 6229 Netherlands;3. Pôle de Chirurgie Expérimentale et Transplantation, Université Catholique de Louvain, Avenue Hippocrate 55/B1.55.04, Woluwe-Saint Lambert, 1200 Belgium
Abstract:Microencapsulating pancreatic islets in immunoprotective alginate hydrogels is a promising strategy for treatment of type 1 diabetes. However, this strategy is limited by inflammation and hypoxia mediated oxidative stress, due to encapsulation and the hydrogel itself, leading to impaired insulin secretion and limited short and long term cell survival. Herein, the antioxidant effect of fucoidan, an algae derived polysaccharide, on beta cells, and its positive effects on encapsulated beta cell viability and function is presented. Fucoidan from Fucus vesiculosus (FF) exhibits a high total antioxidant capacity, and free radical scavenging activity, and is able to significantly alleviate intracellular oxidative stress in rat insolinoma beta cells (INS1E). In addition, FF significantly increases insulin secretion in a dose- and time-dependent manner. When FF is incorporated in ultrapure alginate used for microencapsulation of primary rat islets, both viability and glucose responsiveness of rat islets in these socalled Fucogel microcapsules (Fucocaps) are found to be significantly higher compared to islets encapsulated in alginate alone. Similar results are obtained with INS1E pseudoislets and neonatal pig islets. Fucocaps can provide a redox-modulatory niche and an immune barrier for islets and beta cells in the same time leading to significantly improved survival and endocrine function by mitigating oxidative stress.
Keywords:β-cells  alginate  antioxidant  diabetes type I  fucoidan  microcapsules  pancreatic cells
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