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In the embryo, organs gradually take shape as tissue progenitors, proliferate, differentiate and are organised, via cellular interactions, in tri-dimensional functional structures. Most adult organs retain a cell population sharing important similarities with embryonic progenitors, which includes the ability to both self-renew and to differentiate into the full range of the specialised cell types corresponding to the organ in which they reside. These two essential properties define them as adult stem cells (AdSC). Their characterization in different contexts provides a better understanding of cell turnover modalities for organ function, which is important for tumorigenesis, because adult tissue stem cells can give rise to cancer stem cells. However, it is also relevant to regenerative medicine, because stem cells can be transplanted or manipulated in vivo to restore missing cells. The successful reprogramming of somatic cells into induced pluripotent stem cells (iPSC) (Takahashi and Yamanaka, Cell 126:663–676, 2006), resembling pluripotent embryonic stem cells (ESC), opened alternative strategies for cell replacement. The required cell type can be differentiated in vitro from expandable progenitors and transplanted where required. This approach is particularly promising, because genetic defects can potentially be repaired in vitro prior to their engraftment; moreover, a large number of cells can be produced (Fox et al., Science 345:1247391, 2014). However, the transplanted cells have to be able to functionally integrate into the deficient organ. To potentially alleviate this problem, tri-dimensional culture systems have been recently developed where mini-organs, or organoids, can be obtained in vitro. These also represent unique models for disease modelling and drug screening (Huch and Koo, Development 142:3113–3125, 2015). Within neuroendocrine systems, the hypothalamo-pituitary axis has a crucial role for body homeostasis. It also regulates functions such as growth, reproduction, stress and, more generally, metabolism. The hypothalamus centralizes information from the periphery and other brain regions to regulate pituitary hormone secretions and to control appetite, sleep and aging. Its functions are exerted through secretion of neurohormones and manipulation of these could be of interest not only for the treatment of obesity and sleep disorders but also to alleviate aging-related conditions. Pituitary hormone deficiencies can originate from defects affecting the hypothalamus, pituitary, or both. Today these deficiencies are treated by substitution or replacement therapies, which are costly and have side effects. AdSC have recently been characterized in the hypothalamus and pituitary (Castinetti et al., Endocr Rev 32:453–471, 2011; Bolborea and Dale, Trends Neurosci 36:91–100, 2013). Moreover, hypothalamic neurons and pituitary endocrine cells have been differentiated in vitro from ESC and iPSC and successfully transplanted. These promising routes for development of regenerative medicine to restore or manipulate the function of the hypothalamo-pituitary axis will be discussed here, and further challenges considered.