Image: 3D reconstruction of the human kidney revealing structures that filter waste and interior blood vessels: Credit: Helmholtz Zentrum München / Ertürk lab
A team of researchers led by Ali Ertürk, director of the Institute for Tissue Engineering and Regenerative Medicine at the Helmholtz Institute, has developed a new technique which enabled them to make human organs transparent. Using new microscopy techniques, they revealed the complex structures of the transparent tissues at the cellular level and have created detailed organ maps, which could be used as blueprints for 3D bioprinting artificial human organs in the future.
The researchers had previously developed a technique that allowed them to clear tissue in mouse organs to make them transparent, but the same method could not be used on human organs. The detergents used for tissue clearing in mice did not work on human organs due to the amount of collagen and other insoluble molecules present in the tissues.
To create transparent human tissues, the researchers had to find alternative chemicals that could make small holes in stiff human organs through which detergents could be introduced to render them transparent. A detergent called CHAPS was found to allow them to do just that. Other solutions could then be introduced in the centimeters- thick tissues to turn them into transparent organs.
Making the organs transparent was just one of the challenges. The researchers needed to develop a new laser-scanning microscope that could be used on large tissue samples such as an intact eye, kidney, or brain. The microscope, named Ultramicroscope Blaze, was developed in collaboration with Miltenyi Biotec.
The researchers also needed to create deep learning algorithms to analyze hundreds of millions of cells in the organs in 3D and create organ maps. The algorithms they developed could analyze millions of cells in cleared in a few hours, and only required standard laboratory computers. The researchers named their technique of tissue clearing, imaging, and 3D mapping SHANEL (Small-micelle-mediated Human orgAN Efficient clearing and Labeling).
They used SHANEL to render an intact adult human brain and kidney transparent and performed 3D tissue histology using antibodies and dyes. The researchers also used SHANEL on an intact human eye, thyroid, and transgenic pig pancreas to reveal structural details at the cellular resolution.
“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,” said Ertürk. “Detailed knowledge about the cellular structure of human organs brings us an important step closer to creating functional organs artificially on demand.”
You can read more about the study in the paper – Cellular and Molecular Probing of Intact Human Organs – which was recently published in the journal Cell. DOI: 10.1016/j.cell.2020.01.030