Organoid

Intestinal organoid grown from Lgr5+ stem cells.

An organoid is a three-dimensional organ-bud grown in vitro that shows realistic micro-anatomy. 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]

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 2010, Mathieu Unbekandt & Jamie A. Davies demonstrated the production of renal organoids from murine fetus-derived renogenic stem cells:[4] subsequent reports showed significant physiological function of these organoids in vitro[5] and in vivo.[6]

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.[7] 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.[8]

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[9]

Types of organoids

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.[22] 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.[23] 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

References

  1. ↑ Grens, Kerry (December 24, 2013). "2013’s Big Advances in Science". The Scientist. Retrieved 26 December 2013.
  2. ↑ Yong, Ed (August 28, 2013). "Lab-Grown Model Brains". The Scientist. Retrieved 26 December 2013.
  3. 1 2 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.
  4. ↑ Unbekandt, M.; Davies, J.A. (2010). "Dissociation of embryonic kidneys followed by reaggregation allows the formation of renal tissues". Kidney International 77 (5): 407–416. doi:10.1038/ki.2009.482.
  5. ↑ Lawrence, M.L.; Chang, C.H.; Davies, J.A. (2015). "Transport of organic anions and cations in murine embryonic kidney development and in serially-reaggregated engineered kidneys". Scientific Reports 77 (5): 9092–9092. doi:10.1038/srep09092. PMC 4357899.
  6. ↑ Xinaris, C.; Benedetti, V.; Rizzo, P.; Abbate, M.; Corna, D.; Azzolini, N.; Conti, S.; Unbekandt, M.; Davies, J.A.; Morigi, M.; Begnini, A.; Remuzzi, G. (2012). "In vivo maturation of functional renal organoids formed from embryonic cell suspensions". J. Am. Soc. Neprhol. 23 (11): 1857–1868. doi:10.1681/ASN.2012050505. PMC 3482737.
  7. ↑ 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.
  8. ↑ 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.
  9. ↑ 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.
  10. ↑ 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.
  11. ↑ 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.
  12. ↑ 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.
  13. ↑ 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.
  14. ↑ 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.
  15. ↑ 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.
  16. ↑ Unbekandt, M.; Davies, J.A. (2010). "Dissociation of embryonic kidneys followed by reaggregation allows the formation of renal tissues.". Kidney International 77 (5): 407–416. doi:10.1038/ki.2009.482.
  17. ↑ 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.
  18. ↑ 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.
  19. ↑ 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.
  20. ↑ 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.
  21. ↑ 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.
  22. ↑ 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.
  23. ↑ 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.
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