title: Effect of microcapsule composition and short-term immunosuppression on intraportal biocompatibility.
abstract: With higher nutrient and oxygen supply and close contact to blood, the portal vein is a possible alternative to the peritoneal cavity for transplantation of encapsulated cells. Data regarding intraportal biocompatibility of microcapsules are lacking. Microcapsules were built from five alginate types differing in their molar mass and mannuronic/guluronic acid ratios by complex formation with divalent cations (barium or calcium) or mixtures of divalent cations and polycations. They were injected in the portal vein of rats, and cellular and fibrotic pericapsular infiltration thickness was measured 3 and 7 days after implantation. Overgrowth was characterized using various stainings or immunohistochemistry (hematoxylin and eosin, Giemsa, ED-1 for monocyte/macrophage, alpha-actin for myofibroblasts, CD31 for endothelial cells). The impact of short-term immunosuppression (gadolinium-chloride IV 20 mg/kg/day on days--1 and 4 as well as 10 days of rapamycin PO 1 mg/kg/day, tacrolimus PO 3 mg/kg/day, or combinations of rapamycin/tacrolimus or gadolinium/tacrolimus) was further assessed 3, 7, and 42 days after implantation. Overall, overgrowth increased from day 3 to day 7 (p < 0.05). Three and 7 days after implantation, polycation-containing microcapsules induced more reaction than microbeads (p < 0.0001 and p < 0.01). Considering polycation-free beads, barium-alginate induced the weakest reaction. Biocompatibility of microbeads was independent of mannuronic/guluronic acid ratio and molar mass of the alginate. Infiltration was mainly a monocyte/macrophage-rich foreign body reaction, but an eosinophil-containing immunoallergic reaction was also observed. Short-term immunosuppression significantly reduced infiltration in all conditions and up to 42 days after implantation. Biocompatibility after intraportal infusion was best for barium-alginate microbeads and poorest for polycation-containing microcapsules. Short- and long-term overgrowth could be significantly reduced by short-term immunosuppression.
authors.affiliation: Centre d'isolement et de transplantation cellulaire, Service de chirurgie viscérale, Hôpital Universitaire, 4, rue Micheli-du-Crest, CH-1211 Geneva 14, Switzerland. christian.toso@hcuge.ch
authors.forename: Christian
authors.initials: C
authors.lastname: Toso
authors.forename: Zoltan
authors.initials: Z
authors.lastname: Mathe
authors.forename: Philippe
authors.initials: P
authors.lastname: Morel
authors.forename: José
authors.initials: J
authors.lastname: Oberholzer
authors.forename: Domenico
authors.initials: D
authors.lastname: Bosco
authors.forename: Dianelys
authors.initials: D
authors.lastname: Sainz-Vidal
authors.forename: David
authors.initials: D
authors.lastname: Hunkeler
authors.forename: Leo H
authors.initials: LH
authors.lastname: Buhler
authors.forename: Christine
authors.initials: C
authors.lastname: Wandrey
authors.forename: Thierry
authors.initials: T
authors.lastname: Berney
mesh_terms: D000464:Alginates / Q000737:chemistry; D000818:Animals; D001672:Biocompatible Materials / Q000008:administration & dosage* / Q000737:chemistry; D002214:Capsules / Q000008:administration & dosage* / Q000737:chemistry; D020723:Glucuronic Acid / Q000737:chemistry; D006603:Hexuronic Acids / Q000737:chemistry; D007165:Immunosuppression Therapy / Q000379:methods; D008297:Male; D008422:Materials Testing; D011168:Portal System / Q000166:cytology; D019736:Prostheses and Implants; D051381:Rats; D011917:Rats, Inbred Lew
chemical_list: D000464:Alginates; D001672:Biocompatible Materials; D002214:Capsules; D006603:Hexuronic Acids; D020723:Glucuronic Acid; C008324:mannuronic acid