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Intestinal organoid grown from Lgr5+ stem cells.
An organoid is a three-dimensional organ-bud grown in vitro. The technique for growing organoids has rapidly improved since the early 2010s, and it was named by The Scientist as one of the biggest scientific advancements of 2013.[1]
Contents
- 1 History
- 2 Types of organoids
- 3 Organoid models of disease
- 4 Further reading
- 5 References
History
In 2008, Yoshiki Sasai and his team at RIKEN institute demonstrated that stem cells can be coaxed into balls of neural cells that self-organize into distinctive layers.[2] In 2009 the Laboratory of Hans Clevers at Hubrecht Institute and University Medical Center Utrecht, The Netherlands showed that single LGR5 stem cells build crypt-villus structures in vitro without a mesenchymal niche.[3]
In 2013, Madeline Lancaster at the Austrian Academy of Sciences established a protocol for culturing cerebral organoids derived from stem cells that mimic the developing human brain's cellular organization.[4] In 2014, Artem Shkumatov et al. at the University of Illinois at Urbana-Champaign demonstrated that cardiovascular organoids can be formed from ES cells through modulation of the substrate stiffness, to which they adhere. Physiological stiffness promoted three-dimensionality of EBs and cardiomyogenic differentiation.[5]
Takebe et al. demonstrate a generalized method for organ bud formation from diverse tissues by combining pluripotent stem cell-derived tissue-specific progenitors or relevant tissue samples with endothelial cells and mesenchymal stem cells (MSCs). They suggested that the less mature tissues, or organ buds, generated through the self-organized condensation principle might be the most efficient approach toward the reconstitution of mature organ functions after transplantation, rather than condensates generated from cells of a more advanced stage[6]
Types of organoids
- Cerebral organoid
- Thyroid organoid[7]
- Intestinal Organoid
- Testicular Organoid
- Hepatic Organoid[8]
- Pancreatic Organoid[9]
- Gastric Organoid[10]
- Epithelial Organoid[3][11]
- Lung Organoid[12]
- Kidney Organoid[13][14][15]
- Embryonic (Gastruloids)[16][17]
Organoid models of disease
Organoids provide an opportunity to create cellular models of human disease, which can be studied in the laboratory to better understand the causes of disease and identify possible treatments. In one example, the genome editing system called CRISPR was applied to human pluripotent stem cells to introduce targeted mutations in genes relevant to two different kidney diseases, polycystic kidney disease and focal segmental glomerulosclerosis.[18] These CRISPR-modified pluripotent stem cells were subsequently grown into human kidney organoids, which exhibited disease-specific phenotypes. Kidney organoids from stem cells with polycystic kidney disease mutations formed large, translucent cyst structures from kidney tubules. Kidney organoids with mutations in a gene linked to focal segmental glomerulosclerosis developed junctional defects between podocytes, the filtering cells affected in that disease. Importantly, these disease phenotypes were absent in control organoids of identical genetic background, but lacking the CRISPR mutations.[19] These experiments demonstrate how organoids can be utilized to create complex models of human disease in the laboratory, which recapitulate tissue-level phenotypes in a petri dish.
Further reading
- Willyard, Cassandra (2015). "The boom in mini stomachs, brains, breasts, kidneys and more". Nature 523: 520–522. doi:10.1038/523520a.
- Kelly Rae Chi (2015). Orchestrating Organoids. A guide to crafting tissues in a dish that reprise in vivo organs. The Scientist.
- Takebe, T., Enomura, M., Yoshizawa, E., Kimura, M., Koike, H., Ueno, Y., ... & Taniguchi, H. (2015). Vascularized and Complex Organ Buds from Diverse Tissues via Mesenchymal Cell-Driven Condensation. Cell stem cell, 16(5), 556-565. DOI:10.1016/j.stem.2015.03.004
- Turner DA, Baillie-Johnson P, Martinez Arias, A (2016). "Organoids and the genetically encoded self-assembly of embryonic stem cells". Bioassays 38 (2): 181-91. doi: 10.1002/bies.201500111
References
- ^ Kerry Grens (December 24, 2013). "2013’s Big Advances in Science". The Scientist. Retrieved 26 December 2013.
- ^ Ed Yong (August 28, 2013). "Lab-Grown Model Brains". The Scientist. Retrieved 26 December 2013.
- ^ a b Sato, Toshiro; Vries, Robert G.; Snippert, Hugo J.; Van De Wetering, Marc; Barker, Nick; Stange, Daniel E.; Van Es, Johan H.; Abo, Arie; Kujala, Pekka; Peters, Peter J.; Clevers, Hans (2009). "Single Lgr5 stem cells build cryptvillus structures in vitro without a mesenchymal niche". Nature 459 (7244): 262–5. Bibcode:2009Natur.459..262S. doi:10.1038/nature07935. PMID 19329995.
- ^ Chambers, Stuart M.; Tchieu, Jason; Studer, Lorenz (October 2013). "Build-a-Brain". Cell Stem Cell 13 (4): 377–8. doi:10.1016/j.stem.2013.09.010. PMID 24094317.
- ^ Shkumatov, A; Baek, K; Kong, H (2014). "Matrix Rigidity-Modulated Cardiovascular Organoid Formation from Embryoid Bodies". PLoS ONE 9 (4): e94764. Bibcode:2014PLoSO...994764S. doi:10.1371/journal.pone.0094764. PMC 3986240. PMID 24732893.
- ^ Takebe, T.; Enomura, M.; Yoshizawa, E.; Kimura, M.; Koike, H.; Ueno, Y.; Taniguchi, H. (2015). "Vascularized and Complex Organ Buds from Diverse Tissues via Mesenchymal Cell-Driven Condensation". Cell stem cell 16 (5): 556–565. doi:10.1016/j.stem.2015.03.004.
- ^ Martin, Andreas; Barbesino, Giuseppe; Davies, Terry F. (1999). "T-Cell Receptors and Autoimmune Thyroid Disease—Signposts for T-Cell-Antigen Driven Diseases". International Reviews of Immunology 18 (1–2): 111–40. doi:10.3109/08830189909043021. PMID 10614741.
- ^ Huch, M; Gehart, H; Van Boxtel, R; Hamer, K; Blokzijl, F; Verstegen, M. M.; Ellis, E; Van Wenum, M; Fuchs, S. A.; De Ligt, J; Van De Wetering, M; Sasaki, N; Boers, S. J.; Kemperman, H; De Jonge, J; Ijzermans, J. N.; Nieuwenhuis, E. E.; Hoekstra, R; Strom, S; Vries, R. R.; Van Der Laan, L. J.; Cuppen, E; Clevers, H (2015). "Long-Term Culture of Genome-Stable Bipotent Stem Cells from Adult Human Liver". Cell 160 (1–2): 299–312. doi:10.1016/j.cell.2014.11.050. PMC 4313365. PMID 25533785.
- ^ Huch, M; Bonfanti, P; Boj, S. F.; Sato, T; Loomans, C. J.; Van De Wetering, M; Sojoodi, M; Li, V. S.; Schuijers, J; Gracanin, A; Ringnalda, F; Begthel, H; Hamer, K; Mulder, J; Van Es, J. H.; De Koning, E; Vries, R. G.; Heimberg, H; Clevers, H (2013). "Unlimited in vitro expansion of adult bi-potent pancreas progenitors through the Lgr5/R-spondin axis". The EMBO Journal 32 (20): 2708–2721. doi:10.1038/emboj.2013.204. PMC 3801438. PMID 24045232.
- ^ Stange, D. E.; Koo, B. K.; Huch, M; Sibbel, G; Basak, O; Lyubimova, A; Kujala, P; Bartfeld, S; Koster, J; Geahlen, J. H.; Peters, P. J.; Van Es, J. H.; Van De Wetering, M; Mills, J. C.; Clevers, H (2013). "Differentiated Troy+ chief cells act as 'reserve' stem cells to generate all lineages of the stomach epithelium". Cell 155 (2): 357–368. doi:10.1016/j.cell.2013.09.008. PMC 4094146. PMID 24120136.
- ^ Barker, Nick; Van Es, Johan H.; Kuipers, Jeroen; Kujala, Pekka; Van Den Born, Maaike; Cozijnsen, Miranda; Haegebarth, Andrea; Korving, Jeroen; Begthel, Harry; Peters, Peter J.; Clevers, Hans (2007). "Identification of stem cells in small intestine and colon by marker gene Lgr5". Nature 449 (7165): 1003–7. Bibcode:2007Natur.449.1003B. doi:10.1038/nature06196. PMID 17934449.
- ^ Lee, Joo-Hyeon; Bhang, Dong Ha; Beede, Alexander; Huang, Tian Lian; Stripp, Barry R.; Bloch, Kenneth D.; Wagers, Amy J.; Tseng, Yu-Hua; Ryeom, Sandra. "Lung Stem Cell Differentiation in Mice Directed by Endothelial Cells via a BMP4-NFATc1-Thrombospondin-1 Axis". Cell 156 (3): 440–455. doi:10.1016/j.cell.2013.12.039. ISSN 0092-8674. PMC 3951122. PMID 24485453.
- ^ Takasato, Minoru; Er, Pei X.; Chiu, Han S.; Maier, Barbara; Baillie, Gregory J.; Ferguson, Charles; Parton, Robert G.; Wolvetang, Ernst J.; Roost, Matthias S. "Kidney organoids from human iPS cells contain multiple lineages and model human nephrogenesis". Nature 526 (7574): 564–568. doi:10.1038/nature15695.
- ^ Freedman, BS; Brooks, CR; Lam, AQ; Fu, H; Morizane, R; Agrawal, V; Saad, AF; Li, MK; Hughes, MR; Werff, RV; Peters, DT; Lu, J; Baccei, A; Siedlecki, AM; Valerius, MT; Musunuru, K; McNagny, KM; Steinman, TI; Zhou, J; Lerou, PH; Bonventre, JV (23 October 2015). "Modelling kidney disease with CRISPR-mutant kidney organoids derived from human pluripotent epiblast spheroids.". Nature communications 6: 8715. doi:10.1038/ncomms9715. PMID 26493500.
- ^ Morizane, Ryuji; Lam, Albert; Freedman, Benjamin; Kishi, Seiji; Valerius, Todd; Bonventre, Joseph. "Nephron organoids derived from human pluripotent stem cells model kidney development and injury.". Nature Biotechnology 33 (11): 1193–1200. doi:10.1038/nbt.3392.
- ^ van den Brink, Susanne C.; Baillie-Johnson, Peter; Balayo, Tina; Hadjantonakis, Anna-Katerina; Nowotschin, Sonja; Turner, David A.; Martinez Arias, Alfonso (2014-11-01). "Symmetry breaking, germ layer specification and axial organisation in aggregates of mouse embryonic stem cells". Development (Cambridge, England) 141 (22): 4231–4242. doi:10.1242/dev.113001. ISSN 1477-9129. PMC 4302915. PMID 25371360.
- ^ Turner, David A.; Baillie-Johnson, Peter; Martinez Arias, Alfonso (2016-02-01). "Organoids and the genetically encoded self-assembly of embryonic stem cells". BioEssays: News and Reviews in Molecular, Cellular and Developmental Biology 38 (2): 181–191. doi:10.1002/bies.201500111. ISSN 1521-1878. PMID 26666846.
- ^ Freedman, BS; Brooks, CR; Lam, AQ; Fu, H; Morizane, R; Agrawal, V; Saad, AF; Li, MK; Hughes, MR; Werff, RV; Peters, DT; Lu, J; Baccei, A; Siedlecki, AM; Valerius, MT; Musunuru, K; McNagny, KM; Steinman, TI; Zhou, J; Lerou, PH; Bonventre, JV (23 October 2015). "Modelling kidney disease with CRISPR-mutant kidney organoids derived from human pluripotent epiblast spheroids.". Nature communications 6: 8715. PMID 26493500.
- ^ Freedman, BS; Brooks, CR; Lam, AQ; Fu, H; Morizane, R; Agrawal, V; Saad, AF; Li, MK; Hughes, MR; Werff, RV; Peters, DT; Lu, J; Baccei, A; Siedlecki, AM; Valerius, MT; Musunuru, K; McNagny, KM; Steinman, TI; Zhou, J; Lerou, PH; Bonventre, JV (23 October 2015). "Modelling kidney disease with CRISPR-mutant kidney organoids derived from human pluripotent epiblast spheroids.". Nature communications 6: 8715. PMID 26493500.
UpToDate Contents
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English Journal
- Primary mouse small intestinal epithelial cell cultures.
- Sato T, Clevers H.SourceDepartment of Gastroenterology, School of Medicine, Keio University, Tokyo, Japan, T.sato@a7.keio.jp.
- Methods in molecular biology (Clifton, N.J.).Methods Mol Biol.2013;945:319-28. doi: 10.1007/978-1-62703-125-7_19.
- The intestinal epithelium is the most rapidly self-renewing tissue in adult mammals. We have recently shown that Lgr5 (Leucine-rich repeat-containing G protein-coupled receptor) is expressed in intestinal stem cells by an in vivo genetic lineage tracing strategy. In the past, extensive efforts have
- PMID 23097115
- Controlled formation of heterotypic hepatic micro-organoids in anisotropic hydrogel microfibers for long-term preservation of liver-specific functions.
- Yamada M, Utoh R, Ohashi K, Tatsumi K, Yamato M, Okano T, Seki M.SourceDepartment of Applied Chemistry and Biotechnology, Graduate School of Engineering, Chiba University, 1-33 Yayoi-cho, Inage-ku, Chiba 263-8522, Japan.
- Biomaterials.Biomaterials.2012 Nov;33(33):8304-15. doi: 10.1016/j.biomaterials.2012.07.068. Epub 2012 Aug 17.
- We have developed a hydrogel-based cell cultivation platform for forming 3D restiform hepatic micro-organoids consisting of primary rat hepatocytes and feeder cells (Swiss 3T3 cells). Sodium alginate solutions containing hepatocytes/3T3 cells were continuously introduced into a microfluidic channel
- PMID 22906609
Japanese Journal
- 未分化型早期胃癌における適応拡大条件と粘液組織学的検討 (特集 未分化型早期胃癌の診断とESDの適応)
- 根本 利恵子,楢原 進一郎,瀬戸山 充
- 西日本皮膚科 = The Nishinihon journal of dermatology : 日本皮膚科学会西部支部機関誌 76(1), 23-26, 2014-02
- NAID 40019972005
- Wntシグナルによる消化器上皮幹細胞制御 (内分泌) -- (基礎分野での進歩)
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- organoid /or·ga·noid/ (or´gah-noid) 1. resembling an organ. 2. a structure that resembles an organ. or·gan·oid (ôr′gə-noid′) adj. Resembling an organ. n. See organelle. organoid [ôr′gənoid] Etymology: Gk, organon + eidos, form 1 adj, resembling an organ.
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