Studies on Smaller (~315 μM) Microcapsules: IV. Feasibility and Safety of Intrahepatic Implantations of Small Alginate Poly-L-Lysine Microcapsules

Abstract

The most successful transplantation site of nonencapsulated islets of Langerhans is the liver. Because usual alginate poly-L-lysine microcapsules were too large (700–1200 μm diameter) for intravascular implantations and were almost exclusively implanted intraperitoneally, the question of the preferred implantation site of microencapsulated islets has received little attention. The feasibility of implanting smaller (~315 μm) alginate poly-L-lysine microcapsules into the liver and the effect of such implantations on portal pressure and liver histology was evaluated in Wistar rats. A bolus of 10,000 microcapsules of 315 μm diameter was injected intraportally (group 1; n = 22). The portal pressure increased from 6.4 ± 1.8 mmHg to a maximum of 19 mmHg, returned to basal levels within 2 h, and remained normal after 2 months. In group 2 (n = 3), following the injection of 10,000 larger microcapsules (420 μm), the portal pressure increased to > 60 mmHg and two out of the three rats died within 3 h. When 5,000 microcapsules of 420-μm diameter were injected (group 3; n = 5), the portal pressure peaked to 30 ± 8 mmHg and remained elevated after 4 h (12 ± 3 mmHg), but returned to normal (8 ± 1 mmHg) after 2 weeks. Histological studies showed normal hepatic architecture without collagen deposition into portal tracts occupied by microcapsules. Conclusion: intrahepatic implantations of ~315-μm alginate poly-L-lysine microcapsules are feasible and safe. These results justify further investigation of this potential implantation site for microencapsulated islets.