Studies on smaller (similar to 315 mu M) microcapsules: IV. Feasibility and safety of intrahepatic implantations of small alginate poly-L-lysine microcapsules

The most successful transplantation site of nonencapsulated islets of Lange rhans is the liver. Because usual alginate poly-L-lysine microcapsules were too large (700-1200 mu m diameter) for intravascular implantations and wer e almost exclusively implanted intraperitoneally, the question of the prefe rred implantation site of microencapsulated islets has received little atte ntion. The feasibility of implanting smaller (similar to 315 mu m) alginate poly-L-lysine microcapsules into the liver and the effect of such implanta tions on portal pressure and liver histology was evaluated in Wistar rats. A bolus of 10,000 microcapsules of 315 mu m diameter was injected intraport ally (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 10,0 00 larger microcapsules (420 mu m), the portal pressure increased to > 60 m mHg and two out of the three rats died within 3 h. When 5,000 microcapsules of 420-mu m diameter were injected (group 3; n = 5), the portal pressure p eaked 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 show ed normal hepatic architecture without collagen deposition into portal trac ts occupied by microcapsules. Conclusion: intrahepatic implantations of sim ilar to 315-mu m alginate poly-L-lysine microcapsules are feasible and safe . These results justify further investigation of this potential implantatio n site for microencapsulated islets.