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

• Published in: Diabetes (New York, N.Y.) Vol. 70; no. Supplement_1
• Main Authors: BACHUL, PIOTR J., GENERETTE, GABRIELA S., PYDA, JORDAN S., BOREK, PETER, PEREZ-GUTIERREZ, ANGELICA, GOLAB, KAROLINA, BASTO, LINDSAY, PEREA, LAURENCIA, TIBUDAN, MARTIN, JUENGEL, BRADEN, KUMAR, JAYANT, THOMAS, CELESTE C., PHILIPSON, LOUIS H., FUNG, JOHN, WITKOWSKI, PIOTR
• Format: Journal Article
• Language: English
• Published: New York American Diabetes Association 01.06.2021
• Subjects: Abdomen; Abdominal wall; Allografts; Blood levels; Diabetes; Dosage; Glucose; Glucose monitoring; Immunosuppression; Insulin; Mycophenolic acid; Pancreatic islet transplantation; Patients; Peptides; Safety; Tacrolimus; Thymoglobulin; Vascularization
• ISSN: 0012-1797; 1939-327X
• DOI: 10.2337/db21-1146-P

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 1st and 2nd ITx into SCP. After 2nd 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 2nd 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. Disclosure P. J. Bachul: None. B. Juengel: None. J. Kumar: None. C. C. Thomas: None. L. H. Philipson: Advisory Panel; Self; Nevro Corp., Research Support; Self; Provention Bio, Inc. J. Fung: None. P. Witkowski: None. G. S. Generette: None. J. S. Pyda: None. P. Borek: None. A. Perez-gutierrez: None. K. Golab: None. L. Basto: None. L. Perea: None. M. Tibudan: None. Funding JDRF; Sernova, Corp.