title: Macroporous biohybrid cryogels for co-housing pancreatic islets with mesenchymal stromal cells.
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.
  
  
  
  Diabetes results in the insufficient production of insulin by the pancreatic β-cells in the islets of Langerhans. Transplantation of pancreatic islets offers valuable options for treating the disease; however, many transplanted islets often do not survive the transplantation or die shortly thereafter. Co-transplanted, supporting cells and biomaterials can be instrumental for improving islet survival, function and protection from the immune system. In the present study, islet supportive hydrogel sponges were explored for the co-transplantation of islets and mesenchymal stromal cells. Survival and continued function of the supported islets were demonstrated in vitro. The in vivo feasibility of the approach was shown by transplantation in a mouse model.
authors: 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.
authors: Danielle J
authors: DJ
authors: Borg
authors: Leibniz Institute of Polymer Research Dresden, Max Bergmann Center of Biomaterials Dresden, Hohe Str. 6, 01069 Dresden, Germany. Electronic address: welzel@ipfdd.de.
authors: Petra B
authors: PB
authors: Welzel
authors: Leibniz Institute of Polymer Research Dresden, Max Bergmann Center of Biomaterials Dresden, Hohe Str. 6, 01069 Dresden, Germany. Electronic address: grimmer@ipfdd.de.
authors: Milauscha
authors: M
authors: Grimmer
authors: Leibniz Institute of Polymer Research Dresden, Max Bergmann Center of Biomaterials Dresden, Hohe Str. 6, 01069 Dresden, Germany. Electronic address: friedrichs@ipfdd.de.
authors: Jens
authors: J
authors: Friedrichs
authors: 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.
authors: Marc
authors: M
authors: Weigelt
authors: 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.
authors: Carmen
authors: C
authors: Wilhelm
authors: Leibniz Institute of Polymer Research Dresden, Max Bergmann Center of Biomaterials Dresden, Hohe Str. 6, 01069 Dresden, Germany. Electronic address: mc.prewitz@googlemail.com.
authors: Marina
authors: M
authors: Prewitz
authors: Leibniz Institute of Polymer Research Dresden, Max Bergmann Center of Biomaterials Dresden, Hohe Str. 6, 01069 Dresden, Germany. Electronic address: alinestissel@web.de.
authors: Aline
authors: A
authors: Stißel
authors: 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.
authors: Angela
authors: A
authors: Hommel
authors: 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.
authors: Thomas
authors: T
authors: Kurth
authors: Leibniz Institute of Polymer Research Dresden, Max Bergmann Center of Biomaterials Dresden, Hohe Str. 6, 01069 Dresden, Germany. Electronic address: freudenberg@ipfdd.de.
authors: Uwe
authors: U
authors: Freudenberg
authors: 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.
authors: Ezio
authors: E
authors: Bonifacio
authors: Leibniz Institute of Polymer Research Dresden, Max Bergmann Center of Biomaterials Dresden, Hohe Str. 6, 01069 Dresden, Germany. Electronic address: werner@ipfdd.de.
authors: Carsten
authors: C
authors: Werner
mesh_terms: D000818:Animals; D001672:Biocompatible Materials / Q000494:pharmacology*; D002470:Cell Survival / Q000187:drug effects; D059985:Cryogels / Q000494:pharmacology*; D006493:Heparin / Q000737:chemistry; D007328:Insulin / Q000378:metabolism; D000078790:Insulin Secretion; D007515:Islets of Langerhans / Q000166:cytology* / Q000187:drug effects; D016381:Islets of Langerhans Transplantation; D045164:Mesenchymal Stem Cell Transplantation; D059630:Mesenchymal Stem Cells / Q000166:cytology* / Q000187:drug effects; D008810:Mice, Inbred C57BL; D011092:Polyethylene Glycols / Q000737:chemistry; D016062:Porosity; D034421:Sus scrofa; D023822:Tissue Engineering; D054457:Tissue Scaffolds / Q000737:chemistry; D014185:Transplantation, Isogeneic
chemical_list: D001672:Biocompatible Materials; D059985:Cryogels; D007328:Insulin; D011092:Polyethylene Glycols; D006493:Heparin
keywords: Cryogel; Heparin; Mesenchymal stromal cell; Pancreatic islet; Poly(ethylene glycol)