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 o f immunosuppression. The aim of this study was to investigate the problem o f overgrowth on implanted capsules with regard to the composition of the ca psules 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 o xidation rates showed the metabolic activity of the cellular overgrowth on retrieved capsules. DNA content, histological score, and retrieval rates we re also measured to assess the overgrowth. It was noted that the pericapsul ar host reaction arose by day 7 and had not increased further by day 28. Ca psules 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 positivel y correlated to each other and negatively correlated to retrieval rates. Th e 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 cellul ar overgrowth on implanted capsules and had reduced mRNA expression of inte rleukin-lp and turner necrosis factor-alpha in their peritoneal macrophages . The capsular overgrowth seemed more severe in animals lacking inducible n itric oxide synthase compared with wild-type controls. It is concluded that alginate composition, PLL, and recipient factors such as nitric oxide prod uction and cytokine expression affect the cellular overgrowth on implanted alginate capsules. (C) 2001 John Wiley & Sons, Inc.