title: Long-term Efficacy and Biocompatibility of Encapsulated Islet Transplantation With Chitosan-Coated Alginate Capsules in Mice and Canine Models of Diabetes.
abstract: BACKGROUND
  Clinical application of encapsulated islet transplantation is hindered by low biocompatibility of capsules leading to pericapsular fibrosis and decreased islet viability. To improve biocompatibility, we designed a novel chitosan-coated alginate capsules and compared them to uncoated alginate capsules.
  
  
  METHODS
  Alginate capsules were formed by crosslinking with BaCl2, then they were suspended in chitosan solution for 10 minutes at pH 4.5. Xenogeneic islet transplantation, using encapsulated porcine islets in 1,3-galactosyltransferase knockout mice, and allogeneic islet transplantation, using encapsulated canine islets in beagles, were performed without immunosuppressants.
  
  
  RESULTS
  The chitosan-alginate capsules showed similar pore size, islet viability, and insulin secretory function compared to alginate capsules, in vitro. Xenogeneic transplantation of chitosan-alginate capsules demonstrated a trend toward superior graft survival (P = 0.07) with significantly less pericapsular fibrosis (cell adhesion score: 3.77 ± 0.41 vs 8.08 ± 0.05; P < 0.001) compared to that of alginate capsules up to 1 year after transplantation. Allogeneic transplantation of chitosan-alginate capsules normalized the blood glucose level up to 1 year with little evidence of pericapsular fibrotic overgrowth on graft explantation.
  
  
  CONCLUSIONS
  The efficacy and biocompatibility of chitosan-alginate capsules were demonstrated in xenogeneic and allogeneic islet transplantations using small and large animal models of diabetes. This capsule might be a potential candidate applicable in the treatment of type 1 diabetes mellitus patients, and further studies in nonhuman primates are required.
authors.affiliation: 1 Division of Endocrinology and Metabolism, Department of Internal Medicine, College of Medicine, The Catholic University of Korea, Seoul, South Korea. 2 Division of Endocrinology and Metabolism, Department of Internal Medicine, Seoul St. Mary's Hospital, Seoul, South Korea. 3 Department of BIN Fusion Technology and Department of Polymer Nano-Science Technology, Chonbuk National University, Jeollabuk-do, South Korea. 4 Department of Surgery, Seoul St. Mary's Hospital, College of Medicine, The Catholic University of Korea, Seoul, South Korea.
authors.forename: Hae Kyung
authors.initials: HK
authors.lastname: Yang
authors.forename: Dong-Sik
authors.initials: DS
authors.lastname: Ham
authors.forename: Heon-Seok
authors.initials: HS
authors.lastname: Park
authors.forename: Marie
authors.initials: M
authors.lastname: Rhee
authors.forename: Young Hye
authors.initials: YH
authors.lastname: You
authors.forename: Min Jung
authors.initials: MJ
authors.lastname: Kim
authors.forename: Juyoung
authors.initials: J
authors.lastname: Shin
authors.forename: On-You
authors.initials: OY
authors.lastname: Kim
authors.forename: Gilson
authors.initials: G
authors.lastname: Khang
authors.forename: Tae Ho
authors.initials: TH
authors.lastname: Hong
authors.forename: Ji-Won
authors.initials: JW
authors.lastname: Kim
authors.forename: Seung-Hwan
authors.initials: SH
authors.lastname: Lee
authors.forename: Jae-Hyoung
authors.initials: JH
authors.lastname: Cho
authors.forename: Kun-Ho
authors.initials: KH
authors.lastname: Yoon
mesh_terms: D000464:Alginates / Q000737:chemistry*; D000818:Animals; D017609:Barium Compounds / Q000737:chemistry; D001786:Blood Glucose / Q000378:metabolism; D002448:Cell Adhesion; D048271:Chitosan / Q000737:chemistry*; D002712:Chlorides / Q000737:chemistry; D020099:Coated Materials, Biocompatible; D003432:Cross-Linking Reagents / Q000737:chemistry; D003921:Diabetes Mellitus, Experimental / Q000097:blood / Q000473:pathology / Q000601:surgery*; D003922:Diabetes Mellitus, Type 1 / Q000097:blood / Q000473:pathology / Q000601:surgery*; D004285:Dogs; D005260:Female; D005355:Fibrosis; D005700:Galactosyltransferases / Q000172:deficiency / Q000235:genetics; D020723:Glucuronic Acid / Q000737:chemistry; D006085:Graft Survival; D064593:Heterografts; D006603:Hexuronic Acids / Q000737:chemistry; D007328:Insulin / Q000097:blood; D007515:Islets of Langerhans / Q000378:metabolism / Q000473:pathology / Q000601:surgery*; D016381:Islets of Langerhans Transplantation / Q000009:adverse effects / Q000379:methods*; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D016062:Porosity; D000067996:RAW 264.7 Cells; D013552:Swine; D013556:Swine, Miniature; D013997:Time Factors; D014184:Transplantation, Homologous
chemical_list: D000464:Alginates; D017609:Barium Compounds; D001786:Blood Glucose; D002712:Chlorides; D020099:Coated Materials, Biocompatible; D003432:Cross-Linking Reagents; D006603:Hexuronic Acids; D007328:Insulin; C024986:barium chloride; D020723:Glucuronic Acid; D048271:Chitosan; D005700:Galactosyltransferases