Encapsulated stem cell–derived β cells exert glucose control in patients with type 1 diabetes

• Published in: Nature biotechnology Vol. 42; no. 10; pp. 1507 - 1514
• Main Authors: Keymeulen, Bart, De Groot, Kaat, Jacobs-Tulleneers-Thevissen, Daniel, Thompson, David M., Bellin, Melena D., Kroon, Evert J., Daniels, Mark, Wang, Richard, Jaiman, Manasi, Kieffer, Timothy J., Foyt, Howard L., Pipeleers, Daniel
• Format: Journal Article
• Language: English
• Published: New York Nature Publishing Group US 01.10.2024; Nature Publishing Group
• Subjects: 631/532/1360; 692/699/2743/137/1418; Adult; Agriculture; Beta cells; Bioinformatics; Biomedical and Life Sciences; Biomedical Engineering/Biotechnology; Biomedicine; Biotechnology; Blood Glucose - metabolism; C-Peptide - blood; C-Peptide - metabolism; Diabetes; Diabetes mellitus (insulin dependent); Diabetes Mellitus, Type 1 - blood; Diabetes Mellitus, Type 1 - drug therapy; Dosage; Embryo cells; Encapsulation; Female; Glucose; Glucose monitoring; Humans; Insulin; Insulin - therapeutic use; Insulin-Secreting Cells - drug effects; Insulin-Secreting Cells - metabolism; Life Sciences; Male; Patients; Peptides; Stem cells
• ISSN: 1087-0156; 1546-1696; 1546-1696
• DOI: 10.1038/s41587-023-02055-5

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. β cells derived from stem cells improve blood glucose control in patients with diabetes.