The effect of host factors and capsule composition on the cellular overgrowth on implanted alginate capsules.
Microencapsulation of islets of Langerhans in alginate/poly-L-lysine (PLL)/alginate capsules may provide a method for transplantation in the absence of immunosuppression. The aim of this study was to investigate the problem of overgrowth on implanted capsules with regard to the composition of the capsules and host factors such as cytokine and nitric oxide production. Empty capsules were implanted to C57BL/6 mice for 1, 3, 7, or 28 days. Glucose oxidation rates showed the metabolic activity of the cellular overgrowth on retrieved capsules. DNA content, histological score, and retrieval rates were also measured to assess the overgrowth. It was noted that the pericapsular host reaction arose by day 7 and had not increased further by day 28. Capsules of varying alginate compositions and different concentrations of PLL were implanted for 7 days to either C57BL/6 or Balb/c mice. Capsules were also implanted to mice lacking the inducible nitric oxide synthase enzyme. Glucose oxidation rates, DNA content, and histological score were positively correlated to each other and negatively correlated to retrieval rates. The pericapsular reaction was reduced if PLL was omitted from the capsule or if a high mannuronic acid alginate was used. Balb/c mice had reduced cellular overgrowth on implanted capsules and had reduced mRNA expression of interleukin-1 beta and tumor necrosis factor-alpha in their peritoneal macrophages. The capsular overgrowth seemed more severe in animals lacking inducible nitric oxide synthase compared with wild-type controls. It is concluded that alginate composition, PLL, and recipient factors such as nitric oxide production and cytokine expression affect the cellular overgrowth on implanted alginate capsules.
King
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Department of Medical Cell Biology, Box 571, Biomedical Centre, Uppsala University, SE 751 23 Uppsala, Sweden. aileen.king@medcellbiol.ii.se
Sandler
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Andersson
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D000464:Alginates / Q000737:chemistry*; D000818:Animals; D001672:Biocompatible Materials; D002214:Capsules; D002455:Cell Division / Q000502:physiology; D002469:Cell Separation; D017690:Cell Transplantation / Q000379:methods*; D016207:Cytokines / Q000096:biosynthesis; D004247:DNA / Q000096:biosynthesis; D005549:Foreign-Body Reaction / Q000473:pathology; D007515:Islets of Langerhans / Q000166:cytology; D016381:Islets of Langerhans Transplantation / Q000379:methods*; D007700:Kinetics; D008264:Macrophages / Q000378:metabolism; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D009569:Nitric Oxide / Q000737:chemistry; D019001:Nitric Oxide Synthase / Q000096:biosynthesis; D052247:Nitric Oxide Synthase Type II; D010084:Oxidation-Reduction; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013045:Species Specificity
D000464:Alginates; D001672:Biocompatible Materials; D002214:Capsules; D016207:Cytokines; D009569:Nitric Oxide; D004247:DNA; D019001:Nitric Oxide Synthase; D052247:Nitric Oxide Synthase Type II; C496317:Nos2 protein, mouse