Human pluripotent-derived lineages for repairing hypopituitarism

Abstract

Human pluripotent stem cells (hPSCs) present a potentially unlimited source of specialized cell types for regenerative medicine. Over the last few years there has been rapid progress in realizing this potential by developing protocols to generate disease-relevant cell types in vitro on demand. The approach was particularly successful for the nervous system, where the field is at the verge of human translation for several indications, including the treatment of eye disorders, Parkinson’s disease and spinal cord injury. More recently, there has also been success in deriving anterior pituitary lineages from both mouse and human pluripotent stem cells. In vitro-derived pituitary hormone-producing cell types present an attractive source for repair in patients with hypopituitarism. However, several hurdles remain towards realizing this goal. In particular, there is a need to further improve the efficiency and precision with which specific hormone-producing lineages can be derived. Furthermore, it will be important to assess the potential of both ectopic and orthotopic transplantation strategies to achieve meaningful hormone replacement. The ultimate challenge will be repair that moves beyond hormone replacement towards the full functional integration of the grafted cells into the complex regulatory endocrine network controlled by the human pituitary gland.