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      Macroporous biohybrid cryogels for co-housing pancreatic islets with mesenchymal stromal cells.

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          Abstract

          Intrahepatic transplantation of allogeneic pancreatic islets offers a promising therapy for type 1 diabetes. However, long-term insulin independency is often not achieved due to severe islet loss shortly after transplantation. To improve islet survival and function, extrahepatic biomaterial-assisted transplantation of pancreatic islets to alternative sites has been suggested. Herein, we present macroporous, star-shaped poly(ethylene glycol) (starPEG)-heparin cryogel scaffolds, covalently modified with adhesion peptides, for the housing of pancreatic islets in three-dimensional (3D) co-culture with adherent mesenchymal stromal cells (MSC) as accessory cells. The implantable biohybrid scaffolds provide efficient transport properties, mechanical protection, and a supportive extracellular environment as a desirable niche for the islets. MSC colonized the cryogel scaffolds and produced extracellular matrix proteins that are important components of the natural islet microenvironment known to facilitate matrix-cell interactions and to prevent cellular stress. Islets survived the seeding procedure into the cryogel scaffolds and secreted insulin after glucose stimulation in vitro. In a rodent model, intact islets and MSC could be visualized within the scaffolds seven days after subcutaneous transplantation. Overall, this demonstrates the potential of customized macroporous starPEG-heparin cryogel scaffolds in combination with MSC to serve as a multifunctional islet supportive carrier for transplantation applications.

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          Author and article information

          Journal
          Acta Biomater
          Acta biomaterialia
          Elsevier BV
          1878-7568
          1742-7061
          Oct 15 2016
          : 44
          Affiliations
          [1 ] Preclinical Approaches to Stem Cell Therapy, DFG-Center for Regenerative Therapies Dresden, Dresden University of Technology, Fetscherstrasse 105, Dresden 01307, Germany. Electronic address: danielle.borg@mater.uq.edu.au.
          [2 ] Leibniz Institute of Polymer Research Dresden, Max Bergmann Center of Biomaterials Dresden, Hohe Str. 6, 01069 Dresden, Germany. Electronic address: welzel@ipfdd.de.
          [3 ] Leibniz Institute of Polymer Research Dresden, Max Bergmann Center of Biomaterials Dresden, Hohe Str. 6, 01069 Dresden, Germany. Electronic address: grimmer@ipfdd.de.
          [4 ] Leibniz Institute of Polymer Research Dresden, Max Bergmann Center of Biomaterials Dresden, Hohe Str. 6, 01069 Dresden, Germany. Electronic address: friedrichs@ipfdd.de.
          [5 ] Preclinical Approaches to Stem Cell Therapy, DFG-Center for Regenerative Therapies Dresden, Dresden University of Technology, Fetscherstrasse 105, Dresden 01307, Germany. Electronic address: marc.weigelt@crt-dresden.de.
          [6 ] Preclinical Approaches to Stem Cell Therapy, DFG-Center for Regenerative Therapies Dresden, Dresden University of Technology, Fetscherstrasse 105, Dresden 01307, Germany. Electronic address: carmenzitawilhelm@web.de.
          [7 ] Leibniz Institute of Polymer Research Dresden, Max Bergmann Center of Biomaterials Dresden, Hohe Str. 6, 01069 Dresden, Germany. Electronic address: mc.prewitz@googlemail.com.
          [8 ] Leibniz Institute of Polymer Research Dresden, Max Bergmann Center of Biomaterials Dresden, Hohe Str. 6, 01069 Dresden, Germany. Electronic address: alinestissel@web.de.
          [9 ] Preclinical Approaches to Stem Cell Therapy, DFG-Center for Regenerative Therapies Dresden, Dresden University of Technology, Fetscherstrasse 105, Dresden 01307, Germany. Electronic address: angela.hommel@crt-dresden.de.
          [10 ] Electron Microscopy Facility, DFG-Center for Regenerative Therapies Dresden, Dresden University of Technology, Fetscherstrasse 105, Dresden, 01307, Germany. Electronic address: thomas.kurth@crt-dresden.de.
          [11 ] Leibniz Institute of Polymer Research Dresden, Max Bergmann Center of Biomaterials Dresden, Hohe Str. 6, 01069 Dresden, Germany. Electronic address: freudenberg@ipfdd.de.
          [12 ] Preclinical Approaches to Stem Cell Therapy, DFG-Center for Regenerative Therapies Dresden, Dresden University of Technology, Fetscherstrasse 105, Dresden 01307, Germany. Electronic address: ezio.bonifacio@crt-dresden.de.
          [13 ] Leibniz Institute of Polymer Research Dresden, Max Bergmann Center of Biomaterials Dresden, Hohe Str. 6, 01069 Dresden, Germany. Electronic address: werner@ipfdd.de.
          Article
          S1742-7061(16)30394-4
          10.1016/j.actbio.2016.08.007
          27506126
          b0ab16e8-57cd-4898-b77e-06b5089e6864
          History

          Poly(ethylene glycol),Pancreatic islet,Mesenchymal stromal cell,Heparin,Cryogel

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