In vivo biocompatibility evaluation of cellulose macrocapsules for islet immunoisolation: Implications of low molecular weight cut-off

Earlier we showed the in vitro suitability of cellulose molecular dialysis membrane of low cut-off for islet immunoisolation. Using a syngenic islet transplantation model, here we report the in vivo biocompatibility status and discuss implications of the low molecular weight cut-off of this membrane. Streptozotocin diabetic mice were transplanted ip with islet grafts in cellulose macrocapsules and monitored for 6 weeks for their blood glucose profiles. Membrane biocompatibility was evaluated by assessing islet graft morphometry, viability, functionality, and tissue reaction against the capsules. Animals (n = 10) attained normoglycemia after 1 week of transplantation and remained nondiabetic throughout a follow-up of 6 weeks. Animals subjected to a glucose tolerance test at the end of the study showed delayed glycemic control, indicating a delayed insulin response. Grafts retrieved after the 15(th) day and after 6 weeks showed viable islets, between 70-80% and approximately 40%, respectively, with morphometric parameters similar to freshly isolated islets. Graft retrievals resulted in a recurrence of hyperglycemia, indicating a functional tissue mass. A mild tissue reaction with a few immunocytes and a very thin fibrous capsular reaction were seen against the macrocapsule membrane. This study points out the in vivo suitability of cellulose membrane for islet immunoisolation. However, applicability of this membrane is limited due to its low cut-off value. Membranes with a higher molecular weight cut-off may render better glycemic control and higher graft viability.