Human pluripotent stem cells (hPSCs) and three-dimensional organoids have ushered in a new era for disease modeling and drug discovery. Over the past decade, significant progress has been in deriving functional organoids from hPSCs, which have been applied to recapitulate disease phenotypes. In addition, these advancements have extended the application of hPSCs and organoids for drug screening and clinical-trial safety evaluations. This review provides an overview of the achievements and challenges in using hPSC-derived organoids to conduct relevant high-throughput, high-contentscreens and drug evaluation. These studies have greatly enhanced our knowledge and toolbox for precision medicine.

Cell-based therapies are being developed for various neurodegenerative diseases that affect the central nervous system (CNS). Concomitantly, the roles of individual cell types in neurodegenerative pathology are being uncovered by genetic and single-cell studies. With a greater understanding of cellular contributions to health and disease and with the arrival of promising approaches to modulate them, effective therapeutic cell products are now emerging. This review examines how the ability to generate diverse CNS cell types from stem cells, along with a deeper understanding of cell-type-specific functions and pathology, is advancing preclinical development of cell products for the treatment of neurodegenerative diseases.

The generation of islet-like endocrine clusters from human pluripotent stem cells (hPSCs) has the potential to provide an unlimited source of insulin-producing β cells for the treatment of diabetes. In order for this cell therapy to become widely adopted, highly functional and well-characterized stem cell-derived islets (SC-islets) need to be manufactured at scale. Furthermore, successful SC-islet replacement strategies should prevent significant cell loss immediately following transplantation and avoid long-term immune rejection. This review highlights the most recent advances in the generation and characterization of highly functional SC-islets as well as strategies to ensure graft viability and safety after transplantation.