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Inside the Lab Microscopy and imaging, Histology, Technology and innovation, Neurology

3D Tissue Staining Visualizes Whole Organs

3D tissue imaging holds great promise – but although tissue clearing can produce stunning images, it has little scientific value on its own. To study specific tissue and cell types, a versatile staining and labeling method that works across a range of staining agents and antibodies is needed. A team from Japan have now developed exactly that, using their technique, CUBIC-HistoVIsion, to stain and image not just tissues, but even an entire mouse brain (1). Etsuo Susaki from the RIKEN Center for Biosystems Dynamics Research explains more.

How did you develop the staining method?

By carrying out physical and chemical analyses, we discovered that the physicochemical properties of biological tissue can be recreated in electrolyte gel. Toyoichi Tanaka first described biological tissue as a gel at the Massachusetts Institute of Technology in the 1980s – and we were excited to rediscover his work.

We selected an artificial gel to mimic biological tissue and experimentally evaluated various staining conditions to establish a fine-tuned 3D staining method called CUBIC-HistoVIsion. Our bottom-up design approach works with over 30 different antibodies and nuclear staining agents.

What is the new technique’s significance?

Immunostaining is a powerful way to detect cell types, protein expressions, protein modifications, and protein localization in tissues. 3D imaging can reveal the precise location of these signals with the same level of detail as transcriptomics. The technique can be used to identify new cell states or cellular connections or to collect information on cell types and their positions in the body. It can also be applied to projects such as the Human Cell Atlas or the Human Protein Atlas to assist with mapping locations and relationships.

We have already used our method to compare whole-organ anatomical features among species – including imaging a mouse brain, half a marmoset brain, and a square centimeter of human brain tissue. Our previous work, in which we applied this technique to human lung and lymph node tissues to detect malignancies, has underlined the potential of 3D histopathology (2) – and further research will improve the diagnostic accuracy and objectivity of 3D clinical pathology examination in the future.

Credit: RIKEN institute.

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  1. EA Susaki et al., Nat Commun, 11, 1982 (2020). PMID: 32341345.
  2. S Nojima et al., Sci Rep, 7, 9269 (2017). PMID: 28839164.
About the Author
Luke Turner

While completing my undergraduate degree in Biology, I soon discovered that my passion and strength was for writing about science rather than working in the lab. My master’s degree in Science Communication allowed me to develop my science writing skills and I was lucky enough to come to Texere Publishing straight from University. Here I am given the opportunity to write about cutting edge research and engage with leading scientists, while also being part of a fantastic team!

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