New Study Identifies Five Core Principles Preserving Tissue Structure

The human body undergoes a daily replacement of billions of cells, but the tissues remain flawlessly organized. How can that be?

Image credit: sdecoret/Shutterstock.com

Researchers from the University of Delaware and ChristianaCare’s Helen F. Graham Cancer Center & Research Institute think they have the solution. According to a recent study that was published in the scientific journal Biology of the Cell, the body may be able to preserve the intricate structure of tissues like the colon, for instance, despite the fact that its cells are always dying and being replaced by five fundamental principles.

This study is the result of more than 15 years of collaboration between mathematicians and cancer biologists to uncover the laws governing tissue shape and cellular function.

This may be the biological version of a blueprint, Just like we have a genetic code that explains how our genes work, we may also have a ‘tissue code’ that explains how our bodies stay so precisely organized over time.

Bruce Boman, M.D., Ph.D., Senior Research Scientist, Cawley Center for Translational Cancer Research, ChristianaCare

Math Meets Medicine

The researchers employed mathematical modeling, which is basically a computer simulation of cell behavior, to see whether a limited set of principles could explain the highly ordered structure of the colon lining. It's a great location to learn: The general form and structure of the colon remain relatively constant, but cells regenerate every few days.

The group discovered five fundamental biological principles that seem to control the composition and actions of cells after completing several simulations and improving their models:

• Timing of cell division
• The order in which cells divide
• The direction cells divide and move
• How many times cells divide
• How long a cell lives before it dies

These rules work together like choreography. They control where cells go, when they divide and how long they stick around — and that’s what keeps tissues looking and working the way they should.

Gilberto Schleiniger, PhD, Professor, Department of Mathematical Sciences, University of Delaware

Decoding Human Tissue

The researchers believe that similar rules may apply not only to the colon but to many other tissues throughout the body, including the skin, liver, and brain. If correct, this “tissue code” might help scientists better understand how tissues mend after injury, how birth abnormalities occur, and how illnesses such as cancer arise when the code is interrupted, the mechanisms behind birth defects, and crucially, how diseases like cancer develop when this fundamental code is disrupted.

“Your tissues don’t just grow and shrink randomly. They know what they’re supposed to look like, and they know how to get back to that state, even after damage. That level of precision needs a set of instructions. What we’ve found is a strong candidate for those instructions,” explained Boman.

This finding also has significant implications for the Human Cell Atlas, a global scientific partnership that aims to identify every cell type in the body. While the Atlas seeks to record each cell and what it is doing at any one time, this new study provides a dynamic framework for understanding how those cells remain organized across time.

The results, which reveal basic, universal rules that control cell activity and tissue structure, could help guide future attempts to not only characterize cells but also forecast how they behave in health and disease.

Implications for Disease and Discovery

One reason the researchers used mathematical models over standard biology experiments is that it is incredibly difficult to monitor how each individual cell in a tissue reacts in real time. Researchers may, however, undertake simulations using computer models to discover patterns and dynamics that were previously unseen.

This type of collaboration between biology and mathematics represents a larger shift in how scientists tackle challenging problems. It also corresponds to national priorities: The National Science Foundation’s “Rules of Life” project encourages researchers to discover the underlying rules that regulate living systems. This study is a significant step in that direction.

The team’s next steps will be to verify the model's predictions experimentally, refine them with further data, and investigate their relevance to cancer biology, particularly how disruptions in the tissue code might lead to tumor development or metastasis.

“This is just the beginning. Once you can identify the rules, you can begin to ask entirely new questions, and maybe even learn how to fix what’s gone wrong,” added Schleiniger.