title: A silk-based encapsulation platform for pancreatic islet transplantation improves islet function in vivo.
abstract: The success of pancreatic islet (PI) transplantation is challenged by PI functional damage during the peritransplantation period. A silk-based encapsulation platform including mesenchymal stromal cells (MSCs) was evaluated for islet cell delivery in vivo. Islet equivalents (IEQs) were transplanted into the epididymal fat pads of mice with streptozotocin-induced diabetes. Three PI combinations were tested: (A) co-encapsulated in silk with MSCs; (b) encapsulated in silk alone; or (c) pelleted. Blood glucose levels were monitored and intraperitoneal glucose tolerance test (IPGTT) was performed upon return to euglycaemia. Grafts were removed for histology and cytokine content analysis. Mice with PI grafts in silk showed a prompt return to euglycaemia. IPGTT was significantly improved with PI in silk with MSCs, compared to PI in silk alone or pelleted. Both Th1and Th2cytokines were increased in PI grafts in silk, but Th1cytokines were decreased significantly with PI and MSC co-encapsulation. Histological analysis showed osteogenesis and chondrogenesis in the silk grafts containing MSCs. Future studies will evaluate MSC stability and function in vivo and improve silk biocompatibility for applications in islet transplantation. Copyright © 2015 John Wiley & Sons, Ltd.
authors.affiliation: Department of Pathology, Stanford University School of Medicine, CA, USA.
authors.forename: Diana C
authors.initials: DC
authors.lastname: Hamilton
authors.affiliation: Department of Pathology, Stanford University School of Medicine, CA, USA.
authors.forename: Hank H
authors.initials: HH
authors.lastname: Shih
authors.affiliation: Department of Pathology, Stanford University School of Medicine, CA, USA.
authors.forename: Richard A
authors.initials: RA
authors.lastname: Schubert
authors.affiliation: Department of Pathology, Stanford University School of Medicine, CA, USA.
authors.forename: Sara A
authors.initials: SA
authors.lastname: Michie
authors.affiliation: Department of Pathology, University of Maryland School of Medicine, Baltimore, MD, USA.
authors.forename: Paul N
authors.initials: PN
authors.lastname: Staats
authors.affiliation: Department of Bioengineering, Tufts University, Medford, MA, USA.
authors.forename: David L
authors.initials: DL
authors.lastname: Kaplan
authors.affiliation: Department of Pathology, Stanford University School of Medicine, CA, USA.|Department of Pathology, University of Maryland School of Medicine, Baltimore, MD, USA.
authors.forename: Magali J
authors.initials: MJ
authors.lastname: Fontaine
mesh_terms: D000818:Animals; D001786:Blood Glucose / Q000378:metabolism; D018914:Cells, Immobilized / Q000166:cytology* / Q000187:drug effects; D018925:Chemokines / Q000378:metabolism; D005951:Glucose Tolerance Test; D018836:Inflammation Mediators / Q000378:metabolism; D036341:Intercellular Signaling Peptides and Proteins / Q000378:metabolism; D007515:Islets of Langerhans / Q000187:drug effects / Q000502:physiology*; D016381:Islets of Langerhans Transplantation; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D047011:Silk / Q000494:pharmacology*
chemical_list: D001786:Blood Glucose; D018925:Chemokines; D018836:Inflammation Mediators; D036341:Intercellular Signaling Peptides and Proteins; D047011:Silk
keywords: cell encapsulation; diabetes; hydrogel; immunomodulation; islet; mesenchymal stromal cell; silk; transplantation