A 3D hydrogel model provides a fast and adjustable platform for studying lung cancer biology and evaluating how therapies work, UF Health Cancer Institute researchers have found.
The versatile tool, described in a recent publication in a special issue on cancer and regenerative medicine in the journal Tissue Engineering Part C: Methods, could help researchers better screen therapies for a variety of cancers before they’re tested in animals, boosting research efficiency. It could also help researchers track how a cancer therapy is working, filling gaps between conventional tissue cultures, animals and clinical studies.
“Our goal was to get an understanding of where this model fits in the spectrum of typical preclinical models, from conventional 2D systems to animal models, and we found this 3D hydrogel model could fill a gap in between those,” said Blanka Sharma, Ph.D., an associate professor in the J. Crayton Pruitt Family Department of Biomedical Engineering and the study’s senior author.
A major challenge for studying diseases is that laboratory models don’t always resemble or translate to what happens in animals or people. Sharma’s team saw a need for a tissue culture that resembles human functioning and that researchers could control to understand how small changes in cellular function or the environment impact diseases.
A hydrogel model is like a Jello, with a network of long, cross-linking molecules called polymers that give it structure. The model mimics human tissue characteristics and, importantly, can be adjusted to simulate how tumors behave.
“With a hydrogel, we can create an environment that resembles the mechanical environment that cells see within the body, which makes it useful for studying a number of diseases,” Sharma said. “In cancer, having a 3D environment where we can control things like the stiffness or composition of the tumor provides an advantage over most conventional tissue culture systems.”
The researchers measured the model’s performance in lung cancer, which remains the deadliest cancer in the United States. The new study advances the field of tissue engineering, becoming the first to compare transcriptional profiles produced by a lung cancer hydrogel model with other preclinical models of lung cancer. A transcriptional profile measures gene expression, giving a snapshot of a cell’s function.
After seven days of growing in hydrogels, cells began to resemble those that had been grown for three weeks in an animal, the study found.
“Compared to cancer cells grown in a two-dimensional petri dish, the cells grown in hydrogels had a transcriptional profile that was closer to human tumors growing in the body,” Sharma said.
Researchers ultimately want to use the 3D model to understand how certain immune cells, particularly natural killer cells, interact with cancer cells. The new study showed the hydrogel model successfully mimicked inflammatory pathways and inflammatory signaling, indicating its potential use for those studies, Sharma said.
“We wanted to establish a process that has a lot of tunability in properties, but that is simple and easy enough to be readily adopted by other labs,” Sharma said. “We would love to see more groups interested in using these types of systems to study various mechanisms in cancer biology.”
The team also hopes to expand the work to include patient samples to provide more personalized therapeutic strategies, as well as get a better understanding of why certain patients respond to treatments and others don’t.
The UF Health Cancer Institute’s Biostatistics and Computational Biology Shared Resource team, including co-authors Heather Kates, Ph.D., Kalyanee Shirlekar, M.S., and Jason Brant, Ph.D., performed RNA sequencing and other analyses for the study, which was funded through a Cancer Institute Shared Resources pilot grant, as well as the National Science Foundation and the Leo Clair and Robert Adenbaum Foundation. Suzanne Lightsey, Ph.D., a former graduate student in Sharma’s lab, is the study’s first author.
