By Phoebe Ingraham Renda
As governments in the United States and Europe encourage scientific researchers to work with alternatives to animal models, two University of Pittsburgh researchers say investigators need to start thinking like ecologists.
In a paper published Aug. 19 in Cell Systems, Mo Ebrahimkhani, associate professor of pathology, School of Medicine, and Kamyar Keshavarz, a bioengineering doctoral candidate, Swanson School of Engineering, detailed the parallels between ecological and human biological systems. Together, they proposed a new conceptual and engineering framework called synthetic tissue ecology, aimed at advancing the development of robust multicellular systems for studying disease and regenerative biology. The underlying premise, they say, is that the principles of systems ecology—the study of interactions within and across biological and ecological systems—could be applied as a set of design principles for synthetic tissue construction and engineering.
Like ecosystems, tissues are complex systems composed of diverse environmental interactions nested within multiple biological scales: genes, cells, multicelluar tissues and the whole organism, says Ebrahimkhani. “At each interaction and scale, there’s an emergence of new behaviors that shape the final outcome of the whole complex system,” he said.
Ecology-inspired thinking in cancer research has already proven to be helpful, Keshavarz noted. “A tumor is a dynamic community in which cancer, immune and stromal cells interact with one another and reshape their environment,” he said. “There are already many studies looking at cancer through an ecological lens—examining how these cells compete, cooperate and influence their surroundings—and using this perspective to better understand tumor behavior and develop more effective treatments.”
Currently, novel alternative methods to animal research, such as organoids, computational modeling and synthetic biology, are limited by their fragility and unreliable reproducibility—two issues that, Keshavarz says, must be addressed before researchers can reliably use them for disease modeling or drug screening.
“We think that there is one piece missing in the way we are looking at these multicellular systems that we are making from stem cells,” Keshavarz said. “And that is the interaction between the cells—how cells interact with each other as they grow to form an organoid or a tissue in vitro.”
This synthetic tissue ecology framework, Ebrahimkhani said, can help researchers identify and intentionally engineer cellular communities and interactions that are otherwise missing when tissues are built outside their native, in vivo environment. “By identifying the missing elements, we can then go back and fill those gaps so we can start to build better multicellular systems and better organoids,” he said.