title: Survival of human islets in microbeads containing high guluronic acid alginate crosslinked with Ca2+ and Ba2+.
abstract: BACKGROUND
  The main hurdles to the widespread use of islet transplantation for the treatment of type 1 diabetes continue to be the insufficient number of appropriate donors and the need for immunosuppression. Microencapsulation has been proposed as a means to protect transplanted islets from the host's immune system.
  
  
  METHODS
  This study investigated the function of human pancreatic islets encapsulated in Ca(2+) /Ba(2+) -alginate microbeads intraperitoneally transplanted in diabetic Balb/c mice.
  
  
  RESULTS
  All mice transplanted with encapsulated human islets (n = 29), at a quantity of 3000 islet equivalent (IEQ), achieved normoglycemia 1 day after transplantation and retained normoglycemia for extended periods of time (mean graft survival 134 ± 17 days). In comparison, diabetic Balb/c mice transplanted with an equal amount of non-encapsulated human islets rejected the islets within 2 to 7 days after transplantation (n = 5). Microbeads retrieved after 232 days (n = 3) were found with little to no fibrotic overgrowth and contained viable insulin-positive islets. Immunofluorescent staining on the retrieved microbeads showed F4/80-positive macrophages and alpha smooth muscle actin-positive fibroblasts but no CD3-positive T lymphocytes.
  
  
  CONCLUSIONS
  The Ca(2+) /Ba(2+) -alginate microbeads can protect human islets from xenogeneic rejection in immunocompetent mice without immunosuppression. However, grafts ultimately failed likely secondary to a macrophage-mediated foreign body reaction.
authors.affiliation: Department of Transplant/Surgery, University of Illinois at Chicago, Chicago, IL 60612, USA.
authors.forename: Meirigeng
authors.initials: M
authors.lastname: Qi
authors.forename: Yrr
authors.initials: Y
authors.lastname: Mørch
authors.forename: Igor
authors.initials: I
authors.lastname: Lacík
authors.forename: Kjetil
authors.initials: K
authors.lastname: Formo
authors.forename: Enza
authors.initials: E
authors.lastname: Marchese
authors.forename: Yong
authors.initials: Y
authors.lastname: Wang
authors.forename: Kirstie K
authors.initials: KK
authors.lastname: Danielson
authors.forename: Katie
authors.initials: K
authors.lastname: Kinzer
authors.forename: Shusen
authors.initials: S
authors.lastname: Wang
authors.forename: Barbara
authors.initials: B
authors.lastname: Barbaro
authors.forename: Gabriela
authors.initials: G
authors.lastname: Kolláriková
authors.forename: Dušan
authors.initials: D
authors.lastname: Chorvát
authors.forename: David
authors.initials: D
authors.lastname: Hunkeler
authors.forename: Gudmund
authors.initials: G
authors.lastname: Skjåk-Braek
authors.forename: José
authors.initials: J
authors.lastname: Oberholzer
authors.forename: Berit L
authors.initials: BL
authors.lastname: Strand
mesh_terms: D000464:Alginates / Q000378:metabolism; D000818:Animals; D001464:Barium / Q000378:metabolism; D002118:Calcium / Q000378:metabolism; D003922:Diabetes Mellitus, Type 1 / Q000628:therapy; D004339:Drug Compounding / Q000379:methods*; D020723:Glucuronic Acid / Q000378:metabolism; D006085:Graft Survival / Q000276:immunology / Q000502:physiology*; D006603:Hexuronic Acids / Q000378:metabolism; D006801:Humans; D007165:Immunosuppression Therapy / Q000379:methods; D007515:Islets of Langerhans / Q000166:cytology* / Q000276:immunology; D016381:Islets of Langerhans Transplantation / Q000276:immunology; D051379:Mice; D008807:Mice, Inbred BALB C; D008863:Microspheres
chemical_list: D000464:Alginates; D006603:Hexuronic Acids; C007896:guluronic acid; D001464:Barium; D020723:Glucuronic Acid; D002118:Calcium