Introduction: After the pilot study demonstrated safety of the Sernova Cell Pouch™ (SCP), we modified islet transplantation (ITx) conditions for improved engraftment in the SCP.

Methods: SCPs were implanted in the abdominal anterior rectus sheath of 7 patients with T1DM and problematic hypoglycemia. Immunosuppression was initiated 1 month after SCP implantation and a marginal dose ITx of highly purified islets 1 month later. A second ITx was scheduled 6 to 12 months later. Sentinel SCPs are explanted for histopathology 3 months after ITx. Graft function is monitored by blood glucose (BG), C-peptide and insulin usage.

Results: Seven patients underwent 29 study-related surgeries with wound infection in 2 (6.8%) patients after SCP implantation. One patient discontinued following device excision and the second patient’s infection resolved. SCPs are well tolerated with implant durations exceeding 35 months. Three patients received two ITx into SCPs, resulting in new, measurable islet function documented by detectable levels of stimulated C-peptide. A supplemental, single intraportal ITx was sufficient for the first two patients to achieve ongoing insulin independence and freedom from severe hypoglycemic events for over 24 and 4 months with HbA1c 5.4 and 5.5%, respectively. The third patient discontinued insulin support 2 months after a single supplemental intraportal ITx and presented normal blood glucose control during MMTT on post-transplant day 75 with fasting and peak values of 97 and 142mg/ml, respectively, serum C-peptide of 1.11 and 3.39 ng/ml and HbA1c of 5.8%. Two of the remaining 3 patients developed donor specific antibodies with islet graft failure in the SCP after unintended periods of suboptimal immunosuppression. One patient awaits a second ITx into SCP.

Conclusion: ITx with SCP demonstrates long-term safety in an early subset of trial patients. Ongoing results for transplanted SCPs have led to procedural adjustments to further optimize clinical outcomes.