Aims: The goal of the study was to assess safety, tolerability and effectiveness of the prevascularized Sernova Cell Pouch (SCP) for pancreatic islet transplantation.

Material: Each of 6 patients with T1DM and problematic hypoglycemia received 2 cadaveric islet transplants into SCPs pre-implanted onto the muscles of the abdominal wall. Each transplant involved open surgical access and infusion of islets into two 8-channel SCPs and one mini sentinel SCP. Patient received thymoglobulin/basiliximab for induction, tacrolimus and mycophenolate for maintenance immunosuppression.

Results: SCP implants and the combination of SCP with human cadaveric islets were both well tolerated with current durations exceeding 3 years. Wound infection resulting in device removal occurred after only one of 31 (3.2%) surgical procedures.
Detectable islet function (≥0.3ng/ml peak serum c-peptide in mixed meal tolerance test) was achieved in 4 patients following islet transplant to SCP. It was correlated with transplanted islet mass of ≥3,000 IEQ/kg per procedure. Transplantation of islet mass <3,000 IEQ/kg did not lead to detectable c-peptide secretion. C-peptide was detectable for periods ranging from days up to 12 months after the procedure.
Three patients with suboptimal levels of immunosuppression due to non-compliance experienced antibody mediated rejection based on de novo donor specific antibodies (DSAs). One patient with DSAs had detectable stimulated c-peptide at 90 days post-transplant.
Histological assessment of sentinel SCPs retrieved ≥90 days post-transplant revealed surviving functional islets within vascularized SCP channels via positive immunofluorescence staining of insulin, c-peptide, glucagon and somatostatin in 5 of 6 patients.
Five patients received supplemental intraportal islet transplants (IPITx) and all of them remain insulin independent (>3Y, >1Y, 5M, 4M, 3M). The sixth patient is awaiting an IPITx in the coming months as per protocol.
Safety and dose-response observations from the first cohort of 6 patients led to the implementation of 10-channel SCPs with 50% greater transplant capacity than the 8-channel configuration in a second study cohort. Three patients were recently enrolled in the second cohort and implanted with 10-channel SCPs. Two of them are currently recovering from their first islet transplantation. Belatacept was introduced to maintenance immunosuppression in order to lower dose and toxicity of tacrolimus and myfortic and for improved protection from immunologic rejection.

Conclusions: Interim results confirm long-term safety and tolerability of Cell Pouch for pancreatic islet transplantation with histologically confirmed islet graft survival in five out of six patients.