Researchers created a mouse with transparent skin and organs in hopes of visualizing long-range connections between cells.
The research team demonstrated a simple method for creating opaque organs, bodies, and human tissue without disrupting the cellular structure. The study was published in the July 31 edition of Cell Press. The finding could lead to a better understanding of brain-body interactions and more accurate clinical diagnoses.
"Although the idea of tissue clearing has been around for a century, to our knowledge, this is the first study to perform whole-body clearing, as opposed to first extracting and then clearing organs outside the adult body," said senior study author Viviana Gradinaru of the California Institute of Technology.
Long-distance cellular interactions are linked to a number of biological processes. Until now the ability to make organs transparent in order to allow 3D mapping has been limited to the brain or embryo. Researchers recently developed a brain-clearing technique called CLARITY, which embed tissues into hydrogels to preserve its 3D structure; they then use detergents to extract the lipids that make the tissue opaque.
In this new study the researchers worked to make CLARITY available for the entire body. They identified the optimal hydrogel that allows detergents to most quickly remove lipids from the tissue; this sped up the clearing process. The researchers also created something called perfusion-assisted agent release in situ (PARS), which allowed them to administer the clearing agents directly to the rodents' bloodstreams. The method cleared the entire body within two weeks.
The new method allowed the researchers to analyze intact cell connections as well as the structure of molecules within single cells.
"Our easy-to-use tissue clearing protocols, which employ readily available and cost-effective reagents and equipment, will make the subcellular interrogation of large tissue samples an accessible undertaking within the broader research and clinical communities," Gradinaru said.