Neuronal cell-based medicines from pluripotent stem cells: Development, production, and preclinical assessment

Brain degeneration and damage is difficult to cure due to the limited endogenous repair capability of the central nervous system. Furthermore, drug development for treatment of diseases of the central nervous system remains a major challenge. However, it now appears that using human pluripotent stem cell-derived neural cells to replace degenerating cells provides a promising cell-based medicine for rejuvenation of brain function. Accordingly, a large number of studies have carried out preclinical assessments, which have involved different neural cell types in several neurological diseases. Recent advances in animal models identify the transplantation of neural derivatives from pluripotent stem cells as a promising path toward the clinical application of cell therapies [Stem Cells Transl Med 2019;8:681-693; Drug Discov Today 2019;24:992-999; Nat Med 2019;25:1045-1053]. Some groups are moving toward clinical testing in humans. However, the difficulty in selection of valuable critical quality criteria for cell products and the lack of functional assays that could indicate suitability for clinical effect continue to hinder neural cell-based medicine development [Biologicals 2019;59:68-71]. In this review, we summarize the current status of preclinical studies progress in this area and outline the biological characteristics of neural cells that have been used in new developing clinical studies. We also discuss the requirements for translation of stem cell-derived neural cells in examples of stem cell-based clinical therapy.