1146-P: Persistent Graft Function after Islet Allotransplantation Into Prevascularized Sernova Cell Pouch Device: Preliminary Results from the University of Chicago

Introduction: Pre-vascularized Sernova Cell Pouch (SCP) device was developed to provide an optimal environment for cell/islet engraftment in the extravascular space. A first-in-human pilot study showed SCP safety/islet vascularization; however, conditions did not allow detectable islet function. We present preliminary results of phase I/II study testing safety and efficacy of modified SCPs in islet allotransplantation (ITx).

Material and Methods: 6 patients with longstanding T1DM and multiple severe hypoglycemic events (SHEs) were enrolled. Immunosuppression (Thymoglobulin, Tacrolimus, and Mycophenolate) was initiated 3 weeks after abdominal wall SCP surgical implantation. ITx occurred at 3 weeks and 6 months after implantation. Sentinel SCPs were explanted for histopathological evaluation 3 months after transplant. Islet graft function was assessed based on continuous glucose monitoring (CGM), c-peptide, and insulin requirement.

Results: First patient presented with persistent stimulated serum c-peptide at 6 months after 1^st and 2^nd ITx into SCP. After 2^nd ITx, glucose control improved substantially reaching optimal target values for CGM with only 5% of Time Below Range (TBR). Second patient at 3 months after 2^nd ITx had positive stimulated serum c-peptide (0.48 ng/mL) with reduction of HbA1c from 10.6% to 7.6%, decreased insulin requirement from 49 to 28 u/day, improved CGM with TBR <4%, and reduction in Time Above Range (from 75% to 48%). Two patients await ITx and evaluation.

Conclusion: Persistent islet graft function with sustained blood levels of c-peptide, reduction of HbA1c, improved CGM parameters, reduction of SHEs, and decreased total daily insulin requirement was achieved in first 2 patients after ITx into abdominal wall SCPs. Modified approaches, including suspending islets in serum, optimizing islets/dose, and smaller pellet volumes, will likely improve engraftment and outcomes.