Mapping Human Organs by Making Them Transparent

In a study published yesterday in Cell, researchers managed to make intact human organs transparent. Then, using microscopic imaging, the scientists could reveal underlying complex structures of the see-through organs at the cellular level. The resulting organ maps can serve as templates for 3D-bioprinting technologies, which, in the future, could lead to the creation of on-demand artificial organs for patients in need of transplants.

“There is a huge shortage of organ donors for hundreds of thousands of people,” says senior author Ali Ertürk of Helmholtz Zentrum München. “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.”

However, 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 have allowed researchers to visualize transparent mouse organs at the cellular level in 3D, but these methods have not been applicable to human organs.

Human organs are particularly stiff due to the accumulation of insoluble molecules in tissues over years or even decades. Thus, detergents that make mouse organs transparent do not work on human organs. “We had to change our approach completely and start from scratch to find new chemicals that can make human organs transparent,” says first author Shan Zhao of Helmholtz Zentrum München.

At last, the team discovered that a detergent called CHAPS could make small holes throughout stiff human organs. CHAPS allows additional solutions to travel deep into the organs to convert them into a transparent structure.

To image the transparent organs, the team developed a new laser-scanning microscope with a large sample-holding capacity called “Ultramicroscope Blaze” in collaboration with Miltenyi Biotec. Next, the team developed deep learning algorithms that could analyze hundreds of millions of cells in 3D. The researchers named this new technology SHANEL (Small-micelle-mediated Human orgAN Efficient clearing and Labeling).

“SHANEL can develop into a key technology for mapping intact human organs in the near future,” Ertürk explains. “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, Ertürk and his team are currently working on mapping major human organs, starting with the pancreas, heart, and kidney.

Image: Condensed light traveling end-to-end in a transparent human brain made visible with SHANEL. Image courtesy of Helmholtz Zentrum München / Ertürk lab.