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3DISCO (stands for “3D imaging of solvent-cleared organs“)[1] is a histological method that make biological samples more transparent (so called “cleared”) by using series of organic solvents for matching the refractive index (RI) of the tissues with that of the surrounding medium. Structures in transparent tissues can be examined by fluorescence microscopy, without the need for time-consuming physical sectioning and subsequent reconstruction in silico.

The method was developed by the team of Ali Ertürk and Hans-Ulrich Dodt at the Max-Planck-Institute in Munich,[1][2] and it was aimed primarily at clearing and imaging unsectioned mouse brain and spinal cord samples. Later on, the original method or modified versions of it were successfully used in many fields of biological research to image and investigate whole body of mice,[3] structure and function within the mouse brain,[1] stem cells,[4][5] tumor tissues,[6][7][8] developmental processes,[9][10] or whole human embryos.[11]

  1. ^ a b c Ertürk, Ali; Becker, Klaus; Jährling, Nina; Mauch, Christoph P; Hojer, Caroline D; Egen, Jackson G; Hellal, Farida; Bradke, Frank; Sheng, Morgan (November 2012). "Three-dimensional imaging of solvent-cleared organs using 3DISCO". Nature Protocols. 7 (11): 1983–1995. doi:10.1038/nprot.2012.119. ISSN 1750-2799. PMID 23060243. S2CID 2882746.
  2. ^ Ertürk, Ali; Mauch, Christoph P.; Hellal, Farida; Förstner, Friedrich; Keck, Tara; Becker, Klaus; Jährling, Nina; Steffens, Heinz; Richter, Melanie (2011-12-25). "Three-dimensional imaging of the unsectioned adult spinal cord to assess axon regeneration and glial responses after injury". Nature Medicine. 18 (1): 166–171. doi:10.1038/nm.2600. ISSN 1546-170X. PMID 22198277. S2CID 16100638. Archived from the original on 2020-09-15. Retrieved 2019-12-05.
  3. ^ Pan, Chenchen; Cai, Ruiyao; Quacquarelli, Francesca Paola; Ghasemigharagoz, Alireza; Lourbopoulos, Athanasios; Matryba, Paweł; Plesnila, Nikolaus; Dichgans, Martin; Hellal, Farida (October 2016). "Shrinkage-mediated imaging of entire organs and organisms using uDISCO". Nature Methods. 13 (10): 859–867. doi:10.1038/nmeth.3964. ISSN 1548-7105. PMID 27548807. S2CID 3521504. Archived from the original on 2020-09-15. Retrieved 2019-12-05.
  4. ^ Espinosa-Medina, I.; Outin, E.; Picard, C. A.; Chettouh, Z.; Dymecki, S.; Consalez, G. G.; Coppola, E.; Brunet, J.-F. (2014-07-04). "Neurodevelopment. Parasympathetic ganglia derive from Schwann cell precursors". Science. 345 (6192): 87–90. doi:10.1126/science.1253286. ISSN 1095-9203. PMID 24925912. S2CID 206556861.
  5. ^ Acar, Melih; Kocherlakota, Kiranmai S.; Murphy, Malea M.; Peyer, James G.; Oguro, Hideyuki; Inra, Christopher N.; Jaiyeola, Christabel; Zhao, Zhiyu; Luby-Phelps, Katherine (2015-10-01). "Deep imaging of bone marrow shows non-dividing stem cells are mainly perisinusoidal". Nature. 526 (7571): 126–130. Bibcode:2015Natur.526..126A. doi:10.1038/nature15250. ISSN 1476-4687. PMC 4850557. PMID 26416744.
  6. ^ Garofalo, Stefano; D'Alessandro, Giuseppina; Chece, Giuseppina; Brau, Frederic; Maggi, Laura; Rosa, Alessandro; Porzia, Alessandra; Mainiero, Fabrizio; Esposito, Vincenzo (2015-03-30). "Enriched environment reduces glioma growth through immune and non-immune mechanisms in mice". Nature Communications. 6: 6623. Bibcode:2015NatCo...6.6623G. doi:10.1038/ncomms7623. ISSN 2041-1723. PMC 4389244. PMID 25818172.
  7. ^ Oshimori, Naoki; Oristian, Daniel; Fuchs, Elaine (2015-02-26). "TGF-β promotes heterogeneity and drug resistance in squamous cell carcinoma". Cell. 160 (5): 963–976. doi:10.1016/j.cell.2015.01.043. ISSN 1097-4172. PMC 4509607. PMID 25723170.
  8. ^ Tanaka, Nobuyuki; Kanatani, Shigeaki; Tomer, Raju; Sahlgren, Cecilia; Kronqvist, Pauliina; Kaczynska, Dagmara; Louhivuori, Lauri; Kis, Lorand; Lindh, Claes (October 2017). "Whole-tissue biopsy phenotyping of three-dimensional tumours reveals patterns of cancer heterogeneity". Nature Biomedical Engineering. 1 (10): 796–806. doi:10.1038/s41551-017-0139-0. ISSN 2157-846X. PMID 31015588. S2CID 3328035.
  9. ^ Lafkas, Daniel; Shelton, Amy; Chiu, Cecilia; de Leon Boenig, Gladys; Chen, Yongmei; Stawicki, Scott S.; Siltanen, Christian; Reichelt, Mike; Zhou, Meijuan (2015-12-03). "Therapeutic antibodies reveal Notch control of transdifferentiation in the adult lung". Nature. 528 (7580): 127–131. Bibcode:2015Natur.528..127L. doi:10.1038/nature15715. ISSN 1476-4687. PMID 26580007. S2CID 4446653.
  10. ^ Renier, Nicolas; Wu, Zhuhao; Simon, David J.; Yang, Jing; Ariel, Pablo; Tessier-Lavigne, Marc (2014-11-06). "iDISCO: a simple, rapid method to immunolabel large tissue samples for volume imaging". Cell. 159 (4): 896–910. doi:10.1016/j.cell.2014.10.010. ISSN 1097-4172. PMID 25417164.
  11. ^ Belle, Morgane; Godefroy, David; Couly, Gérard; Malone, Samuel A.; Collier, Francis; Giacobini, Paolo; Chédotal, Alain (2017-03-23). "Tridimensional Visualization and Analysis of Early Human Development". Cell. 169 (1): 161–173.e12. doi:10.1016/j.cell.2017.03.008. ISSN 1097-4172. PMID 28340341.

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3DISCO

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3DISCO (stands for “3D imaging of solvent-cleared organs“) is a histological method that make biological samples more transparent (so called “cleared”)...

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Light sheet fluorescence microscopy

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Special tissue clearing techniques have been developed for this purpose, e.g. 3DISCO, CUBIC and CLARITY. Depending on the index of refraction of the cleared...

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CLARITY

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found in gels used for western blots. Brainbow Diffusion Tensor Imaging 3DISCO Chung K, Wallace J, Kim SY, Kalyanasundaram S, Andalman AS, Davidson TJ...

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CUBIC

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their high viscosity. Also, in comparison with solvent based methods like 3DISCO the CUBIC as method based on simple diffusion is still take slightly longer...

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