Encapsulated stem cell–derived β cells exert glucose control in patients with type 1 diabetes
Bart Keymeulen, Kaat De Groot, Daniel Jacobs‐Tulleneers‐Thevissen, David Thompson, Melena D. Bellin, Evert Kroon, Mark Daniels, Richard M. Wang, Manasi Jaiman, Timothy J. Kieffer, Howard L. Foyt, Daniël Pipeleers
Abstract
Abstract Clinical studies on the treatment of type 1 diabetes with device-encapsulated pancreatic precursor cells derived from human embryonic stem cells found that insulin output was insufficient for clinical benefit. We are conducting a phase 1/2, open-label, multicenter trial aimed at optimizing cell engraftment (ClinicalTrials.gov identifier: NCT03163511 ). Here we report interim, 1-year outcomes in one study group that received 2–3-fold higher cell doses in devices with an optimized membrane perforation pattern. β cell function was measured by meal-stimulated plasma C-peptide levels at 3-month intervals, and the effect on glucose control was assessed by continuous glucose monitoring (CGM) and insulin dosing. Of 10 patients with undetectable baseline C-peptide, three achieved levels ≥0.1 nmol l −1 from month 6 onwards that correlated with improved CGM measures and reduced insulin dosing, indicating a glucose-controlling effect. The patient with the highest C-peptide (0.23 nmol l −1 ) increased CGM time-in-range from 55% to 85% at month 12; β cell mass in sentinel devices in this patient at month 6 was 4% of the initial cell mass, indicating directions for improving efficacy.