Creating and imaging transparent human organs

German researchers have managed to make intact human organs transparent, and subsequently used microscopic imaging to reveal the underlying complex structures of these organs at the cellular level. The resulting organ maps could serve as templates for 3D-bioprinting technologies, which could in future lead to the creation of on-demand artificial organs for patients in need.

Deciphering the structural complexity of human organs has always been a major challenge due to the lack of technologies to image them at the cellular level. Recent developments in tissue clearing have allowed researchers to obtain cellular views of intact transparent mouse organs in 3D, but these methods were not applicable to human organs. Indeed, human organs are particularly stiff due to accumulation of insoluble molecules including collagen in tissues that have grown for years or even decades. Thus, traditional detergents that are used for making mouse organs transparent do not work on human organs, particularly adult ones.

“We had to change our approach completely and start from scratch to find new chemicals which can make human organs transparent,” said Shan Zhao, PhD student at Helmholtz Zentrum München and first author of a new study published in the journal Cell.

Joining forces with Ludwig Maximilians University Munich (LMU Munich) and the Technical University of Munich (TUM), Zhao and his team discovered that a detergent called CHAPS could make small holes throughout the entire stiff human organs. CHAPS allows additional solutions to travel deep into centimetres-thick human organs and convert them into a transparent structure.

Transparent human brain, courtesy of the study authors.

After making the human organs transparent, which were obtained post mortem from Professor Ingo Bechmann’s lab at Leipzig University, the team had to tackle additional challenges for both organ imaging and the analysis of the large amount of resulting data. First, they developed a new laser-scanning microscope with a large sample-holding capacity called ‘Ultramicroscope Blaze’ in collaboration with Miltenyi Biotec. This microscope enabled imaging of human organs as large as the kidney. Next, together with Professor Bjoern Menze from TUM, the team developed deep learning algorithms to be able to analyse hundreds of millions of cells in 3D.

The researchers named this new technology SHANEL (Small-micelle-mediated Human orgAN Efficient clearing and Labeling). As explained by Dr Ali Ertürk from Helmholtz Zentrum Münchenm and LMU Munich, “SHANEL can develop into a key technology for mapping intact human organs in the near future. This would dramatically accelerate our understanding of organs such as the brain, their development and function in health and disease.”

Cellular maps of human organs could be used to engineer large-scale human tissues and organs with emerging 3D-bioprinting technologies. Towards this goal, Dr Ertürk and his team are currently working on mapping major human organs, starting with the pancreas, heart and kidney.

“There is a huge shortage of organ donors for hundreds of thousands of people,” Dr Ertürk said. “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.”

Image caption: Vascular and glomeruli details of the human kidney. Image ©Helmholtz Zentrum München/Ertürk lab.

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