A perfect islet: reviewing recent protocol developments and proposing strategies for stem cell derived functional pancreatic islets

• hPSC-derived pancreatic islets offer a promising alternative to donor islets for diabetes cell replacement therapy, addressing the shortage of cadaveric donors. • Current differentiation protocols vary in efficiency across hESC and hiPSC lines, posing a significant challenge for generating patient-specific β cells. • Emulating pancreatic embryogenesis with specific growth factors and signaling molecules is key to guiding hPSCs toward mature, glucose-responsive insulin-secreting β cells. • Further optimization of protocols and characterization methods is essential to ensure the safety and efficacy of hPSC-derived islets before clinical translation.