title: Short-term immunosuppression reduces fibrotic cellular infiltration around barium-M-alginate microbeads injected intraportally.
abstract: BACKGROUND
  One of the major barriers affecting the viability of encapsulated islets is pericapsular fibrotic infiltration (PFI). This study aimed to design strategies to reduce PFI around intraportally injected alginate microbeads.
  
  
  METHODS
  Empty, highly purified, barium-M-alginate microbeads (400 microm) were injected intraportally into Lewis rats (3000 beads/rat). Rats (n = 9/group) were treated daily with either rapamycine (RAPA; 1 mg/kg/d p.o.), tacrolimus (TAC; 2 mg/kg/d p.o.), a combination of both, or gadolinium-chloride (GdC13, 20 mg/kg/d i.v., at day -1 and day +4). Treatment was discontinued at 10 days. Three rats/group were sacrificed at 3, 7, and 42 days after transplantation. Cellular composition of PFI was evaluated by immunohistochemistry. Severity of the reaction to the beads was determined by measuring the thickness of PFI on histology.
  
  
  RESULTS
  The main cellular components of PFI in the liver were macrophages and myofibroblasts. There was a significant (P <.05) reduction in the thickness of PFI in all treated groups, even 6 weeks after transplantation. Encapsulated rat islets showed excellent insulin response to glucose in vitro, with a stimulation index of 3.6 +/- 2.0.
  
  
  CONCLUSIONS
  Combination of highly purified alginate with short-term immunosuppression reduces fibrotic overgrowth around microbeads injected intraportally.
authors.affiliation: Cell Isolation and Transplantation Center, Geneva University Hospitals, Geneva, Switzerland.
authors.forename: Z
authors.initials: Z
authors.lastname: Mathe
authors.forename: P
authors.initials: P
authors.lastname: Bucher
authors.forename: D
authors.initials: D
authors.lastname: Bosco
authors.forename: A
authors.initials: A
authors.lastname: Andres
authors.forename: C
authors.initials: C
authors.lastname: Fux
authors.forename: C
authors.initials: C
authors.lastname: Toso
authors.forename: J
authors.initials: J
authors.lastname: Oberholzer
authors.forename: C
authors.initials: C
authors.lastname: Wandrey
authors.forename: D
authors.initials: D
authors.lastname: Sainz-Vidal
authors.forename: D
authors.initials: D
authors.lastname: Espinosa
authors.forename: L
authors.initials: L
authors.lastname: Bühler
authors.forename: P
authors.initials: P
authors.lastname: Morel
authors.forename: T
authors.initials: T
authors.lastname: Berney
mesh_terms: D000464:Alginates; D000818:Animals; D002214:Capsules; D005355:Fibrosis / Q000517:prevention & control; D020723:Glucuronic Acid; D006603:Hexuronic Acids; D007165:Immunosuppression Therapy / Q000379:methods; D007166:Immunosuppressive Agents / Q000627:therapeutic use; D007515:Islets of Langerhans / Q000166:cytology*; D016381:Islets of Langerhans Transplantation / Q000276:immunology* / Q000379:methods*; D011168:Portal System; D051381:Rats; D011917:Rats, Inbred Lew
chemical_list: D000464:Alginates; D002214:Capsules; D006603:Hexuronic Acids; D007166:Immunosuppressive Agents; D020723:Glucuronic Acid