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

Area of Science:

• Regenerative Medicine
• Endocrinology
• Stem Cell Biology

Background:

• Previous attempts using device-encapsulated human embryonic stem cell-derived pancreatic precursor cells for type 1 diabetes showed insufficient insulin output.
• Optimizing cell engraftment is crucial for clinical efficacy.

Purpose of the Study:

• To report interim 1-year outcomes of a phase 1/2 trial (NCT03163511) investigating higher cell doses and optimized device membrane perforation for type 1 diabetes treatment.
• To assess beta cell function and glucose control following transplantation of stem cell-derived pancreatic precursor cells.

Main Methods:

• A phase 1/2, open-label, multicenter trial involving patients with type 1 diabetes.
• Administration of 2-3 fold higher cell doses in devices with optimized membrane perforation.
• Monitoring of meal-stimulated plasma C-peptide, continuous glucose monitoring (CGM), and insulin dosing over 12 months.

Main Results:

• Three out of 10 patients with undetectable baseline C-peptide achieved levels ≥0.1 nmol/L from month 6 onwards.
• Achieved C-peptide levels correlated with improved CGM metrics and reduced insulin requirements.
• One patient demonstrated a significant increase in CGM time-in-range (55% to 85% at 12 months) and measurable beta cell mass recovery.

Conclusions:

• Optimized delivery of higher doses of stem cell-derived pancreatic precursor cells can restore partial beta cell function and improve glucose control in type 1 diabetes.
• The study indicates directions for enhancing efficacy, such as further improvements in beta cell mass and function within implanted devices.