To understand how different cells interact within a tissue, it’s important to know how they are organized in 3D space. Spatial information can also uncover different ‘islands’ of cells within a tissue that have different characteristics – which could for example explain why a tumor might only partially respond to a targeted treatment.
Research group leaders at the Princess Máxima Center, Benedetta Artegiani and Delilah Hendriks, are working on a new method to uncover biological information about a tumor directly in its 3D environment.
Tiny slices
To build a 3D picture of a tumor, scientists can use microscopes, aided with a few fluorescent molecules that make particular cells light up. New technologies, such as so-called spatial transcriptomics, allow them to look more deeply at the genetic information. But to do that, they need to cut the tissue up into tiny slices first. That means the tissue is not kept whole, and the 3D resolution is largely missing. Thus, both these existing technologies can miss biological information.
Spatial information without cutting up tissue
To build their 3D tissue maps, Artegiani and Hendriks, working with an international consortium, plan to develop a technique that can provide spatial transcriptomics in 3D space and adapt it to study human tumor tissue. Delilah Hendriks, co-leader of the Artegiani & Hendriks group, explains: ‘We will analyze the unique molecular fingerprint of each individual cancer cell in the tumor – giving information about the activity and location of each cell. But crucially, we won’t chop up the tissue to extract the molecular material in each cell. Instead, we will look at networks of molecular information to extrapolate each cell’s position for our 3D tissue map.’
The project, called Voluminex, is carried out by a consortium of scientists led by the KTH Royal Institute of Technology in Sweden. The team were recently awarded a prestigious Pathfinder Open grant, a funding program from the European Innovation Council under the Horizon Europe scheme. to enable their development of sequencing-based microscopy in 3D tissues.
Future: improving diagnosis and treatment
The Artegiani and Hendriks group plan to implement the new technology to better study the brain tumor organoids generated in their lab. Benedetta Artegiani, co-leader of the Artegiani & Hendriks group: ‘By looking at the spatial information that each cell encodes in its DNA, we hope to develop a low-cost way to make 3D ‘maps’ of tissues like tumors or organoids. This technique could help study how tumor and healthy cells interact and could also be used in the clinic to analyze patient tumors. Right now, we’re optimizing it for our brain tumor models, but it could work for any cancer. Fast, affordable 3D tumor snapshots could improve diagnosis and, in future, even point to new treatments.’
The Voluminex consortium is led by the KTH Royal Institute of Technology in Sweden. The other four partner institutions are the Princess Máxima Center for pediatric oncology, Karolinska Institutet, Single Technologies AB and Sorbonne University. The project was awarded a Pathfinder Open grant totalling €3 million.