Manufacturing clinical-grade human induced pluripotent stem cell-derived beta cells for diabetes treatment.

The unlimited proliferative capacity of human pluripotent stem cells (hPSCs) fortifies it as one of the most attractive sources for cell therapy application in diabetes. In the past two decades, vast research efforts have been invested in developing strategies to differentiate hPSCs into clinically suitable insulin-producing endocrine cells or functional beta cells (ß cells). With the end goal being clinical translation, it is critical for hPSCs and insulin-producing ß cells to be derived, handled, stored, maintained and expanded with clinical compliance. This review focuses on the key processes and guidelines for clinical translation of human induced pluripotent stem cell (hiPSC)-derived ß cells for diabetes cell therapy. Here, we discuss the (1) key considerations of manufacturing clinical-grade hiPSCs, (2) scale-up and differentiation of clinical-grade hiPSCs into ß cells in clinically compliant conditions and (3) mandatory quality control and product release criteria necessitated by various regulatory bodies to approve the use of the cell-based products.

Protocol for the generation of pancreatic and hepatic progenitors from human pluripotent stem cells for gene regulatory assays.

This protocol describes the detailed procedures for utilizing human pluripotent stem cells (hPSCs) for pancreatic progenitor and hepatic differentiation, followed by the application of hPSC-derived cells in a luciferase reporter-based assay to study gene regulation. The generated hPSC-derived cells have been shown to achieve morphologies and gene expression profiles specific to their differentiated cell types, and subsequent luciferase assay has been shown to effectively elucidate the role of disease-relevant gene variants. Therefore, this protocol provides a valuable approach for pancreatic and liver disease modeling. For complete details on the use and execution of this protocol, please refer to Ng et al. (2019).