title: Enhanced function of pancreatic islets co-encapsulated with ECM proteins and mesenchymal stromal cells in a silk hydrogel.
abstract: Pancreatic islet encapsulation within biosynthetic materials has had limited clinical success due to loss of islet function and cell death. As an alternative encapsulation material, a silk-based scaffold was developed to reestablish the islet microenvironment lost during cell isolation. Islets were encapsulated with ECM proteins (laminin and collagen IV) and mesenchymal stromal cells (MSCs), known to have immunomodulatory properties or to enhance islet cell graft survival and function. After a 7 day in vitro encapsulation, islets remained viable and maintained insulin secretion in response to glucose stimulation. Islets encapsulated with collagen IV, or laminin had increased insulin secretion at day 2 and day 7, respectively. A 3.2-fold synergistic improvement in islet insulin secretion was observed when islets were co-encapsulated with MSCs and ECM proteins. Furthermore, encapsulated islets had increased gene expression of functional genes; insulin I, insulin II, glucagon, somatostatin, and PDX-1, and lower expression of the de-differentiation genes cytokeratin 19 and vimentin compared to non-encapsulated cells. This work demonstrates that encapsulation in silk with both MSCs and ECM proteins enhances islet function and with further development may have potential as a suitable platform for islet delivery in vivo.
authors: Department of Pathology, Stanford University School of Medicine, 300 Pasteur Drive, H1402, M/C 5626, Stanford, CA 94305-5626, USA.
authors: Nicolynn E
authors: NE
authors: Davis
authors: Liese N
authors: LN
authors: Beenken-Rothkopf
authors: Annie
authors: A
authors: Mirsoian
authors: Nikola
authors: N
authors: Kojic
authors: David L
authors: DL
authors: Kaplan
authors: Annelise E
authors: AE
authors: Barron
authors: Magali J
authors: MJ
authors: Fontaine
mesh_terms: D000818:Animals; D002454:Cell Differentiation / Q000502:physiology; D002469:Cell Separation; D002470:Cell Survival; D024141:Collagen Type IV / Q000737:chemistry; D003922:Diabetes Mellitus, Type 1 / Q000628:therapy*; D016326:Extracellular Matrix Proteins / Q000737:chemistry*; D005260:Female; D005934:Glucagon / Q000378:metabolism; D005947:Glucose / Q000378:metabolism; D006801:Humans; D020136:Hydrogel, Polyethylene Glycol Dimethacrylate / Q000737:chemistry*; D007328:Insulin / Q000378:metabolism*; D000078790:Insulin Secretion; D007515:Islets of Langerhans / Q000737:chemistry / Q000166:cytology / Q000502:physiology*; D016381:Islets of Langerhans Transplantation / Q000379:methods*; D007797:Laminin / Q000737:chemistry; D059630:Mesenchymal Stem Cells / Q000737:chemistry / Q000166:cytology / Q000502:physiology; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D047011:Silk / Q000737:chemistry*; D013004:Somatostatin / Q000378:metabolism; D054457:Tissue Scaffolds
chemical_list: D024141:Collagen Type IV; D016326:Extracellular Matrix Proteins; D007328:Insulin; D007797:Laminin; D047011:Silk; D020136:Hydrogel, Polyethylene Glycol Dimethacrylate; D013004:Somatostatin; D005934:Glucagon; D005947:Glucose