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Saturday, 15 February 2020

Researchers make human organs transparent to enable 3D mapping down at cellular level

This image shows details of a human kidney that has been made transparent. © Helmholtz Zentrum München / Ertürk Lab


A look inside the organ: For the first time, researchers have succeeded in making human organs completely transparent. Thanks to their process, the complex structure of these tissues can be visualized and analyzed down to the cellular level. This enables accurate mapping of the organs - and could one day help create functional artificial replicas.

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Whether brain , heart or kidney: human organs are incredibly complex. Doctors now know the basic structure and function of these tissues. Deciphering its structure in every detail has always been a challenge. Because technologies to make organ structures visible down to the cellular level were missing.

That should change with so-called tissue clearing. This process makes organs transparent and thus enables complex 3D images of them to be generated. So far, however, this was only possible with tissues from mice. The problem: In the course of time, insoluble molecules such as collagen accumulate in human organ tissue and make it stiff. Common cleaning agents can therefore make mouse organs transparent - but they fail to work on human organs, especially to human tissue in adults.



A look into the brain, kidney and co

Shan Zhao from Helmholtz Zentrum München and her colleagues have now succeeded in making the apparently impossible: They have made intact human organs transparent. "We had to take a completely new path and start all over again to find a chemical that could also make human organs transparent," reports the researcher.

After a series of experiments, the scientists came up with the solution: They found that a detergent called CHAPS can create small holes in the stiff organs. This makes them more permeable to other solutions, which then penetrate the fabric a centimeter deep and convert it into transparent structures. In this way, Zhao's team managed, among other things, a unique look into a human brain and kidney.

For example, SHANEL provides insight into the cellular structures of an intact human eye.© Helmholtz Zentrum München / Ertürk Lab

"Key for mapping"

In order to be able to examine the transparent organs in detail, the researchers developed a new laser scanning microscope with a particularly large recording capacity and a self-learning algorithm. As they report, the microscope can take pictures of entire human organs up to the size of a kidney. The algorithm is then used to analyze the millions of cells imaged.

Zhao and her colleagues summarize their entire method under the name SHANEL (Small-micelle-mediated human organ efficient clearing and labeling). “SHANEL could become a key technology for mapping intact human organs in the near future. This would enable us to quickly understand much better how organs such as our brain develop and how they function in a healthy and diseased state,” explains Zhao's colleague Ali Ertürk.

Alternative to donor organs?

According to the scientists, this will result in exciting new possibilities for 3D printing of organs. Because cellular three-dimensional maps of human organs could in future serve as templates for such artificially produced tissues. To achieve this goal, the team is already working on mapping the most important human organs, starting with the pancreas, heart and kidney.



If one day the detailed replication of human organs succeeds, patients who depend on a donor organ in particular could benefit. "There is a huge shortage of organ donors for hundreds of thousands of people," says Ertürk. "The waiting time for patients and the transplantation costs are a real burden. Detailed knowledge about the cellular structure of human organs brings us an important step closer to creating functional organs artificially on demand." emphasizes the researcher.


Bibliography:

Cellular and Molecular Probing of Intact Human Organs

Shan Zhao, Mihail Ivilinov Todorov, Ruiyao Cai, Hanno Steinke, Elisabeth Kemter, Eckhard Wolf, Jan Lipfert, Ingo Bechmann, Ali Ertürk

Published:February 13, 2020

DOI:https://doi.org/10.1016/j.cell.2020.01.030

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