Hypothalamic–pituitary organoid generation through the recapitulation of organogenesis

Ozaki, Hajime; Suga, Hidetaka; Arima, Hiroshi

doi:10.1111/dgd.12719

Cited by 11 publications

(5 citation statements)

References 63 publications

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“…Similarly, hypothalamic neurons with ventricular-like interfacial features can be derived from human ES and iPS cells; these neurons express oxytocin, vasopressin, corticotropin-releasing hormone (CRH) and thyrotropin-releasing hormone, among others 152 . Directed differentiation protocols are also available to generate specific neuropeptidergic cell subtypes 153 and nucleus-specific hypothalamic organoids [154][155][156] . Organoids expressing molecular markers characteristic of the arcuate nucleus can be generated with iPS cells from healthy donors and patients with Prader-Willi syndrome 154 , displaying transcriptomic dysfunctions consistent with the disorder in vivo.…”

Section: Hypothalamusmentioning

confidence: 99%

Functional bioengineered models of the central nervous system

2023

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The functional complexity of the central nervous system (CNS) is unparalleled in living organisms. Its nested cells, circuits and networks encode memories, move bodies and generate experiences. Neural tissues can be engineered to assemble model systems that recapitulate essential features of the CNS and to investigate neurodevelopment, delineate pathophysiology, improve regeneration and accelerate drug discovery. In this Review, we discuss essential structure–function relationships of the CNS and examine materials and design considerations, including composition, scale, complexity and maturation, of cell biology-based and engineering-based CNS models. We highlight region-specific CNS models that can emulate functions of the cerebral cortex, hippocampus, spinal cord, neural-X interfaces and other regions, and investigate a range of applications for CNS models, including fundamental and clinical research. We conclude with an outlook to future possibilities of CNS models, highlighting the engineering challenges that remain to be overcome.

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Section: Hypothalamusmentioning

confidence: 99%

Functional bioengineered models of the central nervous system

2023

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“…Organoids from normal and regenerating pituitaries formed dense and cystic organoids, respectively, and displayed differences in transcriptome and molecular properties, possibly reflecting the activation state of the stem cells. Other groups have focused on the development of components of the hypothalamic–pituitary axis through the in vitro differentiation of organoids from embryonic stems cells (ESC) and induced pluripotent stem cells (iPSC) [ 45 , 46 ].…”

Section: Pituitarymentioning

confidence: 99%

Three Dimensional Models of Endocrine Organs and Target Tissues Regulated by the Endocrine System

Luca,

Zitzmann,

Bornstein

et al. 2023

Cancers

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Immortalized cell lines originating from tumors and cultured in monolayers in vitro display consistent behavior and response, and generate reproducible results across laboratories. However, for certain endpoints, these cell lines behave quite differently from the original solid tumors. Thereby, the homogeneity of immortalized cell lines and two-dimensionality of monolayer cultures deters from the development of new therapies and translatability of results to the more complex situation in vivo. Organoids originating from tissue biopsies and spheroids from cell lines mimic the heterogeneous and multidimensional characteristics of tumor cells in 3D structures in vitro. Thus, they have the advantage of recapitulating the more complex tissue architecture of solid tumors. In this review, we discuss recent efforts in basic and preclinical cancer research to establish methods to generate organoids/spheroids and living biobanks from endocrine tissues and target organs under endocrine control while striving to achieve solutions in personalized medicine.

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“…Different brain organoids can be on the other hand very different in their specificity to recapitulate either whole brain or specific brain regions such as cortex, hippocampus, thalamus or hypothalamus ( Qian et al, 2016 ; Birey et al, 2017 ; Lancaster et al, 2017 ; Xiang et al, 2019 ; Ozaki et al, 2021 ). In case of cerebral cortex, it is possible to differentiate the most dorsal part of the forebrain (the pallium), that gives rise to glutamatergic neurons, or the ventral one (the subpallium) that gives origin to GABAergic interneurons ( Bagley et al, 2017 ; Birey et al, 2017 ).…”

Section: Brain Organoids As New Experimental Systems For In Vitro Myelination Studiesmentioning

confidence: 99%

Novel in vitro Experimental Approaches to Study Myelination and Remyelination in the Central Nervous System

Marangon

Caporale

Boccazzi

et al. 2021

Front. Cell. Neurosci.

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Myelin is the lipidic insulating structure enwrapping axons and allowing fast saltatory nerve conduction. In the central nervous system, myelin sheath is the result of the complex packaging of multilamellar extensions of oligodendrocyte (OL) membranes. Before reaching myelinating capabilities, OLs undergo a very precise program of differentiation and maturation that starts from OL precursor cells (OPCs). In the last 20 years, the biology of OPCs and their behavior under pathological conditions have been studied through several experimental models. When co-cultured with neurons, OPCs undergo terminal maturation and produce myelin tracts around axons, allowing to investigate myelination in response to exogenous stimuli in a very simple in vitro system. On the other hand, in vivo models more closely reproducing some of the features of human pathophysiology enabled to assess the consequences of demyelination and the molecular mechanisms of remyelination, and they are often used to validate the effect of pharmacological agents. However, they are very complex, and not suitable for large scale drug discovery screening. Recent advances in cell reprogramming, biophysics and bioengineering have allowed impressive improvements in the methodological approaches to study brain physiology and myelination. Rat and mouse OPCs can be replaced by human OPCs obtained by induced pluripotent stem cells (iPSCs) derived from healthy or diseased individuals, thus offering unprecedented possibilities for personalized disease modeling and treatment. OPCs and neural cells can be also artificially assembled, using 3D-printed culture chambers and biomaterial scaffolds, which allow modeling cell-to-cell interactions in a highly controlled manner. Interestingly, scaffold stiffness can be adopted to reproduce the mechanosensory properties assumed by tissues in physiological or pathological conditions. Moreover, the recent development of iPSC-derived 3D brain cultures, called organoids, has made it possible to study key aspects of embryonic brain development, such as neuronal differentiation, maturation and network formation in temporal dynamics that are inaccessible to traditional in vitro cultures. Despite the huge potential of organoids, their application to myelination studies is still in its infancy. In this review, we shall summarize the novel most relevant experimental approaches and their implications for the identification of remyelinating agents for human diseases such as multiple sclerosis.

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Hypothalamic–pituitary organoid generation through the recapitulation of organogenesis

Cited by 11 publications

References 63 publications

Functional bioengineered models of the central nervous system

Functional bioengineered models of the central nervous system

Three Dimensional Models of Endocrine Organs and Target Tissues Regulated by the Endocrine System

Novel in vitro Experimental Approaches to Study Myelination and Remyelination in the Central Nervous System

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