Pituitary Lineage Differentiation from Human Induced Pluripotent Stem Cells in 2D and 3D Cultures

Zhou, Yu; Wilson, Robert R.; Udaiyar, Abinav; McLemore, Jerri L.; Sadri‐Ardekani, Hooman; Criswell, Tracy

doi:10.1089/scd.2021.0354

Cited by 8 publications

(4 citation statements)

References 22 publications

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“…Recent advances have led to the development of pituitary tissue generated organoids, but these are limited to the use of transgenic mouse models as the source 20,21,34 . In addition, there are the reports of mouse nonadherent spheres with stem/progenitor characteristics 35 , and human embryonic stem cell generated spheroids or patient derived tumoroids that also lack a multicellular identify and consist of poorly differentiated cells 22,[36][37][38][39][40] .…”

Section: Discussionmentioning

confidence: 99%

Development of Human Pituitary Adenoma Organoids to Facilitate Effective Targeted Treatments of Cushing's Disease.

Zavros

Chakrabarti

Pandey

et al. 2022

Preprint

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Cushing's disease (CD) is a serious endocrine disorder caused by dysregulated adrenocorticotropic hormone (ACTH)-secreting pituitary tumor that stimulates the adrenal glands to overproduce cortisol. Chronic exposure to excess cortisol has detrimental effects on health, including increased stroke rates, diabetes, obesity, cognitive impairment, anxiety, depression, and death. The first-line treatment for CD is pituitary surgery, which is followed by disease remission. Current surgical remission rates reported range from 47–85% depending on several remission criteria. The lack of specificity, poor tolerability, and low efficacy of the subsequent second-line medical therapies makes CD a medical therapeutic challenge. One major limitation that hinders the development of specific medical therapies is the lack of human relevant model systems that recapitulate the cellular composition of pituitary adenomas. Human pituitary adenoma tissue was harvested during transsphenoidal surgery from CD patients to generate organoids (hPITOs). hPITOs generated from corticotroph, lactotroph, gonadotroph and somatotroph adenomas exhibited morphological diversity among the organoid lines between individual patients and amongst subtypes. The similarity in cell lineages between the organoid line and the patient’s tumor was validated by comparing the neuropathology report to the expression pattern of pituitary adenoma specific markers using spectral flow cytometry and exome sequencing. A high-throughput drug screen demonstrated patient-specific drug responses of hPITOs amongst each adenoma subtype. Generation of induced pluripotent stem cells (iPSCs) from patients carrying germline mutations relevant to CD exhibited dysregulated cell lineage commitment. The human pituitary adenoma organoids represent a novel approach in how we model complex pathologies in CD patients that may enable more effective personalized medicine for these patients.

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Section: Discussionmentioning

confidence: 99%

Development of Human Pituitary Adenoma Organoids to Facilitate Effective Targeted Treatments of Cushing's Disease.

Zavros

Chakrabarti

Pandey

et al. 2022

Preprint

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“…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. In addition, 3D pituitary models 157 , 158 may pave the way for neuroendocrine hybrids 159 . Human iPS cells can also be differentiated into functional hypothalamic–pituitary units that respond to hypoglycaemic conditions by secreting adrenocorticotropic hormone (ACTH), thus recapitulating the CRH–ACTH stress pathway 160 .…”

Section: Region-specific Cns Modelsmentioning

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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“…Taken all these studies together, it appears that differentiation toward corticotropes is the most (and only) efficient path (30% of the obtained organoids contain both LHX3- and ACTH-expressing cells; ( 71 )) presently achieved in these PSC-derived 3D models. Recently, another study attempted to differentiate iPSC-derived pituitary organoids more robustly toward the gonadotrope fate by making some changes to the differentiation protocol (e.g., addition of FGF8, FGF10, and a transforming growth factor-β (TGFβ) inhibitor), but did not succeed ( 106 ). Nevertheless, the PSC-derived organoids showed promising in vivo production of ACTH.…”

Section: Main: Pituitary Organoid Modelsmentioning

confidence: 99%

Organoid models of the pituitary gland in health and disease

Laporte

Vankelecom

2023

Front. Endocrinol.

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The pituitary gland represents the hub of our endocrine system. Its cells produce specific hormones that direct multiple vital physiological processes such as body growth, fertility, and stress. The gland also contains a population of stem cells which are still enigmatic in phenotype and function. Appropriate research models are needed to advance our knowledge on pituitary (stem cell) biology. Over the last decade, 3D organoid models have been established, either derived from the pituitary stem cells or from pluripotent stem cells, covering both healthy and diseased conditions. Here, we summarize the state-of-the-art of pituitary-allied organoid models and discuss applications of these powerful in vitro research and translational tools to study pituitary development, biology, and disease.

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Pituitary Lineage Differentiation from Human Induced Pluripotent Stem Cells in 2D and 3D Cultures

Cited by 8 publications

References 22 publications

Development of Human Pituitary Adenoma Organoids to Facilitate Effective Targeted Treatments of Cushing's Disease.

Development of Human Pituitary Adenoma Organoids to Facilitate Effective Targeted Treatments of Cushing's Disease.

Functional bioengineered models of the central nervous system

Organoid models of the pituitary gland in health and disease

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