Organoids

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Introduction

Organoids overview
Organoids overview[1]

Organoids stem cell derived self-organized three-dimensional in vitro tissue cultures. These cultures have been be manipulated to replicate some of the complexity of an in vivo organ, or to produce only certain types of organ related cells. This stem cell research technique has many potential applications in understanding tissue and organ development, clinical therapeutics and cancer medicine.


Stem Cell Links: Introduction | Timeline | Placental Cord Blood | Adult | Induced pluripotent stem cell | Yamanaka Factors | Somatic Cell Nuclear Transfer | Ethics | Organoids | Adult Human Cell Types | Category:Stem Cell

Some Recent Findings

  • Sliced Human Cortical Organoids for Modeling Distinct Cortical Layer Formation[2] "Human brain organoids provide unique platforms for modeling development and diseases by recapitulating the architecture of the embryonic brain. However, current organoid methods are limited by interior hypoxia and cell death due to insufficient surface diffusion, preventing generation of architecture resembling late developmental stages. Here, we report the sliced neocortical organoid (SNO) system, which bypasses the diffusion limit to prevent cell death over long-term cultures. This method leads to sustained neurogenesis and formation of an expanded cortical plate that establishes distinct upper and deep cortical layers for neurons and astrocytes, resembling the third trimester embryonic human neocortex. Using the SNO system, we further identify a critical role of WNT/β-catenin signaling in regulating human cortical neuron subtype fate specification, which is disrupted by a psychiatric-disorder-associated genetic mutation in patient induced pluripotent stem cell (iPSC)-derived SNOs. These results demonstrate the utility of SNOs for investigating previously inaccessible human-specific, late-stage cortical development and disease-relevant mechanisms."
  • Studying Human Neurodevelopment and Diseases Using 3D Brain Organoids J. Neuroscience 5 February 2020, 40 (6) 1186-1193; DOI: https://doi.org/10.1523/JNEUROSCI.0519-19.2019 "In vitro differentiation of pluripotent stem cells provides a systematic platform to study development and disease. Recent advances in brain organoid technology have created new opportunities to investigate the formation and function of the human brain, under physiological and pathological conditions. Brain organoids can be generated to model the cellular and structural development of the human brain, and allow the investigation of the intricate interactions between resident neural and glial cell types. Combined with new advances in gene editing, imaging, and genomic analysis, brain organoid technology can be applied to address questions pertinent to human brain development, disease, and evolution. However, the current iterations of brain organoids also have limitations in faithfully recapitulating the in vivo processes. In this perspective, we evaluate the recent progress in brain organoid technology, and discuss the experimental considerations for its utilization."
  • Review - Organoids-on-a-chip[3] "Recent studies have demonstrated an array of stem cell-derived, self-organizing miniature organs, termed organoids, that replicate the key structural and functional characteristics of their in vivo counterparts. As organoid technology opens up new frontiers of research in biomedicine, there is an emerging need for innovative engineering approaches for the production, control, and analysis of organoids and their microenvironment. In this Review, we explore organ-on-a-chip technology as a platform to fulfill this need and examine how this technology may be leveraged to address major technical challenges in organoid research. We also discuss emerging opportunities and future obstacles for the development and application of organoid-on-a-chip technology."
  • Review - Organoids by design[4] "Organoids are multicellular structures that can be derived from adult organs or pluripotent stem cells. Early versions of organoids range from simple epithelial structures to complex, disorganized tissues with large cellular diversity. The current challenge is to engineer cellular complexity into organoids in a controlled manner that results in organized assembly and acquisition of tissue function. These efforts have relied on studies of organ assembly during embryonic development and have resulted in the development of organoids with multilayer tissue complexity and higher-order functions. We discuss how the next generation of organoids can be designed by means of an engineering-based narrative design to control patterning, assembly, morphogenesis, growth, and function."
More recent papers  
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Search term: Organoids | Culture Organoid Culture | Kidney Organoids | Pancreas Organoids | Neural Organoids

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Older papers  
  • The use of brain organoids to investigate neural development and disease[5] "Understanding the development and dysfunction of the human brain is a major goal of neurobiology. Much of our current understanding of human brain development has been derived from the examination of post-mortem and pathological specimens, bolstered by observations of developing non-human primates and experimental studies focused largely on mouse models. However, these tissue specimens and model systems cannot fully capture the unique and dynamic features of human brain development. Recent advances in stem cell technologies that enable the generation of human brain organoids from pluripotent stem cells (PSCs) promise to profoundly change our understanding of the development of the human brain and enable a detailed study of the pathogenesis of inherited and acquired brain diseases."
  • Kidney Organoids: A Translational Journey[6] "Human pluripotent stem cells (hPSCs) are attractive sources for regenerative medicine and disease modeling in vitro. Directed hPSC differentiation approaches have derived from knowledge of cell development in vivo rather than from stochastic cell differentiation. Moreover, there has been great success in the generation of 3D organ-buds termed 'organoids' from hPSCs; these consist of a variety of cell types in vitro that mimic organs in vivo. The organoid bears great potential in the study of human diseases in vitro, especially when combined with CRISPR/Cas9-based genome-editing. We summarize the current literature describing organoid studies with a special focus on kidney organoids, and discuss goals and future opportunities for organoid-based studies."
  • Modeling Development and Disease with Organoids[7] "Recent advances in 3D culture technology allow embryonic and adult mammalian stem cells to exhibit their remarkable self-organizing properties, and the resulting organoids reflect key structural and functional properties of organs such as kidney, lung, gut, brain and retina. Organoid technology can therefore be used to model human organ development and various human pathologies 'in a dish." Additionally, patient-derived organoids hold promise to predict drug response in a personalized fashion. Organoids open up new avenues for regenerative medicine and, in combination with editing technology, for gene therapy. The many potential applications of this technology are only beginning to be explored."

Inner Ear Organoids

CHIR-treated aggregates give rise to inner ear organoids harboring mechanosensitive hair cells
CHIR-treated aggregates give rise to inner ear organoids harboring mechanosensitive hair cells[8]

Modulation of Wnt Signaling Enhances Inner Ear Organoid Development in 3D Culture[8]

"Stem cell-derived inner ear sensory epithelia are a promising source of tissues for treating patients with hearing loss and dizziness. We recently demonstrated how to generate inner ear sensory epithelia, designated as inner ear organoids, from mouse embryonic stem cells (ESCs) in a self-organizing 3D culture. Here we improve the efficiency of this culture system by elucidating how Wnt signaling activity can drive the induction of otic tissue. We found that a carefully timed treatment with the potent Wnt agonist CHIR99021 promotes induction of otic vesicles-a process that was previously self-organized by unknown mechanisms. The resulting otic-like vesicles have a larger lumen size and contain a greater number of Pax8/Pax2-positive otic progenitor cells than organoids derived without the Wnt agonist. Additionally, these otic-like vesicles give rise to large inner ear organoids with hair cells whose morphological, biochemical and functional properties are indistinguishable from those of vestibular hair cells in the postnatal mouse inner ear. We conclude that Wnt signaling plays a similar role during inner ear organoid formation as it does during inner ear development in the embryo."

inner ear

Kidney Organoids

Renal glomerulus orgaonids
Renal glomerulus orgaonids[9]

Kidney Organoids: A Translational Journey[6]

"Human pluripotent stem cells (hPSCs) are attractive sources for regenerative medicine and disease modeling in vitro. Directed hPSC differentiation approaches have derived from knowledge of cell development in vivo rather than from stochastic cell differentiation. Moreover, there has been great success in the generation of 3D organ-buds termed 'organoids' from hPSCs; these consist of a variety of cell types in vitro that mimic organs in vivo. The organoid bears great potential in the study of human diseases in vitro, especially when combined with CRISPR/Cas9-based genome-editing. We summarize the current literature describing organoid studies with a special focus on kidney organoids, and discuss goals and future opportunities for organoid-based studies."

renal

Liver Organoids

Prior N, Inacio P & Huch M. (2019). Liver organoids: from basic research to therapeutic applications. Gut , , . PMID: 31300517 DOI.

Günther C, Brevini T, Sampaziotis F & Neurath MF. (2019). What gastroenterologists and hepatologists should know about organoids in 2019. Dig Liver Dis , 51, 753-760. PMID: 30948332 DOI.

liver

Pancreas Organoids

Culture and establishment of self-renewing human and mouse adult liver and pancreas 3D organoids and their genetic manipulation.[10]

"Adult somatic tissues have proven difficult to expand in vitro, largely because of the complexity of recreating appropriate environmental signals in culture. We have overcome this problem recently and developed culture conditions for adult stem cells that allow the long-term expansion of adult primary tissues from small intestine, stomach, liver and pancreas into self-assembling 3D structures that we have termed 'organoids'. We provide a detailed protocol that describes how to grow adult mouse and human liver and pancreas organoids, from cell isolation and long-term expansion to genetic manipulation in vitro. Liver and pancreas cells grow in a gel-based extracellular matrix (ECM) and a defined medium. The cells can self-organize into organoids that self-renew in vitro while retaining their tissue-of-origin commitment, genetic stability and potential to differentiate into functional cells in vitro (hepatocytes) and in vivo (hepatocytes and endocrine cells). Genetic modification of these organoids opens up avenues for the manipulation of adult stem cells in vitro, which could facilitate the study of human biology and allow gene correction for regenerative medicine purposes. The complete protocol takes 1-4 weeks to generate self-renewing 3D organoids and to perform genetic manipulation experiments."

pancreas

Neural Organoids

The use of brain organoids to investigate neural development and disease[5]

"Understanding the development and dysfunction of the human brain is a major goal of neurobiology. Much of our current understanding of human brain development has been derived from the examination of post-mortem and pathological specimens, bolstered by observations of developing non-human primates and experimental studies focused largely on mouse models. However, these tissue specimens and model systems cannot fully capture the unique and dynamic features of human brain development. Recent advances in stem cell technologies that enable the generation of human brain organoids from pluripotent stem cells (PSCs) promise to profoundly change our understanding of the development of the human brain and enable a detailed study of the pathogenesis of inherited and acquired brain diseases."

neural

Testicular Organoids

Sakib S, Goldsmith T, Voigt A & Dobrinski I. (2019). Testicular organoids to study cell-cell interactions in the mammalian testis. Andrology , , . PMID: 31328437 DOI.

testis

References

  1. Xu H, Lyu X, Yi M, Zhao W, Song Y & Wu K. (2018). Organoid technology and applications in cancer research. J Hematol Oncol , 11, 116. PMID: 30219074 DOI.
  2. Qian X, Su Y, Adam CD, Deutschmann AU, Pather SR, Goldberg EM, Su K, Li S, Lu L, Jacob F, Nguyen PTT, Huh S, Hoke A, Swinford-Jackson SE, Wen Z, Gu X, Pierce RC, Wu H, Briand LA, Chen HI, Wolf JA, Song H & Ming GL. (2020). Sliced Human Cortical Organoids for Modeling Distinct Cortical Layer Formation. Cell Stem Cell , , . PMID: 32142682 DOI.
  3. Park SE, Georgescu A & Huh D. (2019). Organoids-on-a-chip. Science , 364, 960-965. PMID: 31171693 DOI.
  4. Takebe T & Wells JM. (2019). Organoids by design. Science , 364, 956-959. PMID: 31171692 DOI.
  5. 5.0 5.1 Di Lullo E & Kriegstein AR. (2017). The use of brain organoids to investigate neural development and disease. Nat. Rev. Neurosci. , 18, 573-584. PMID: 28878372 DOI.
  6. 6.0 6.1 Morizane R & Bonventre JV. (2017). Kidney Organoids: A Translational Journey. Trends Mol Med , 23, 246-263. PMID: 28188103 DOI.
  7. Clevers H. (2016). Modeling Development and Disease with Organoids. Cell , 165, 1586-1597. PMID: 27315476 DOI.
  8. 8.0 8.1 DeJonge RE, Liu XP, Deig CR, Heller S, Koehler KR & Hashino E. (2016). Modulation of Wnt Signaling Enhances Inner Ear Organoid Development in 3D Culture. PLoS ONE , 11, e0162508. PMID: 27607106 DOI.
  9. Held M, Santeramo I, Wilm B, Murray P & Lévy R. (2018). Ex vivo live cell tracking in kidney organoids using light sheet fluorescence microscopy. PLoS ONE , 13, e0199918. PMID: 30048451 DOI.
  10. Broutier L, Andersson-Rolf A, Hindley CJ, Boj SF, Clevers H, Koo BK & Huch M. (2016). Culture and establishment of self-renewing human and mouse adult liver and pancreas 3D organoids and their genetic manipulation. Nat Protoc , 11, 1724-43. PMID: 27560176 DOI.

Journals

Reviews

Merenda A, Fenderico N & Maurice MM. (2020). Wnt Signaling in 3D: Recent Advances in the Applications of Intestinal Organoids. Trends Cell Biol. , 30, 60-73. PMID: 31718893 DOI.

Kyrousi C & Cappello S. (2020). Using brain organoids to study human neurodevelopment, evolution and disease. Wiley Interdiscip Rev Dev Biol , 9, e347. PMID: 31071759 DOI.

Chhibber T, Bagchi S, Lahooti B, Verma A, Al-Ahmed A, Paul MK, Pendyala G & Jayant RD. (2019). CNS organoids: an innovative tool for neurological disease modeling and drug neurotoxicity screening. Drug Discov. Today , , . PMID: 31783130 DOI.

Gopalakrishnan J. (2019). The Emergence of Stem Cell-Based Brain Organoids: Trends and Challenges. Bioessays , 41, e1900011. PMID: 31274205 DOI.

Sakib S, Goldsmith T, Voigt A & Dobrinski I. (2019). Testicular organoids to study cell-cell interactions in the mammalian testis. Andrology , , . PMID: 31328437 DOI.

van den Hurk M & Bardy C. (2019). Single-cell multimodal transcriptomics to study neuronal diversity in human stem cell-derived brain tissue and organoid models. J. Neurosci. Methods , 325, 108350. PMID: 31310823 DOI.

Prior N, Inacio P & Huch M. (2019). Liver organoids: from basic research to therapeutic applications. Gut , , . PMID: 31300517 DOI.

Karzbrun E & Reiner O. (2019). Brain Organoids-A Bottom-Up Approach for Studying Human Neurodevelopment. Bioengineering (Basel) , 6, . PMID: 30669275 DOI.

Articles

Mukherjee N, Nandi S, Ghosh S, Garg S & Ghosh S. (2019). Three-Dimensional Microfluidic Platform with Neural Organoids: Model System for Unraveling Synapses. ACS Chem Neurosci , , . PMID: 31872998 DOI.

Muchnik SK, Lorente-Galdos B, Santpere G & Sestan N. (2019). Modeling the Evolution of Human Brain Development Using Organoids. Cell , 179, 1250-1253. PMID: 31778651 DOI.

Pekkanen-Mattila M, Pelto-Huikko M, Kujala V, Suuronen R, Skottman H, Aalto-Setälä K & Kerkelä E. (2010). Spatial and temporal expression pattern of germ layer markers during human embryonic stem cell differentiation in embryoid bodies. Histochem. Cell Biol. , 133, 595-606. PMID: 20369364 DOI.


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Cite this page: Hill, M.A. (2024, March 19) Embryology Organoids. Retrieved from https://embryology.med.unsw.edu.au/embryology/index.php/Organoids

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