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OSU Researchers Develop new Approach for Studying Tissue Regeneration

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Researchers at Oregon State University have shed new light on the process of tissue regeneration in zebrafish – an advance that may one day help scientists learn to regenerate tissues in humans.

The OSU research team, headed by associate professor Robert L. Tanguay and doctoral researcher Lijoy K. Mathews in the Department of Environmental and Molecular Toxicology, looked at the tissue regeneration response in two-day old embryo zebrafish missing their tail fins. They incubated the fish for three days in each of 2,000 biologically active small molecules, in a "rapid throughput" chemical genetic screening to begin to understand how zebrafish regenerate missing body parts.

They identified 17 chemicals that specifically inhibit fin regeneration, including a group of “glucocorticoids.”

The research is being published this week in the Journal of Biological Chemistry.

"By identifying those molecules that turned the regeneration process on and off, we can learn more about the biochemical pathways that control tissue regeneration," said Mathew. "Once we unravel the process in zebrafish, it should be possible to learn why higher organisms such as humans are unable to regenerate tissues."

Medical research has been trying to solve the mystery of tissue regeneration for decades. Scientists hope one day to be able to regenerate human tissues and organs destroyed by heart disease and cancer, or tissues harmed by trauma such as spinal cord damage.

Using zebrafish is a new way of studying tissue regeneration, explained Tanguay. Most researchers working in the field of regenerative medicine are using human embryonic stem cells to produce different cell types for eventual human tissue replacement. But stem cell research has been fraught with slow progress and controversy. So Tanguay, Mathews and their colleagues chose to go a different route and study tissue regeneration in zebrafish.

Zebrafish are commonly used to understand basic developmental and physiological studies because as vertebrates, they share many physiological characteristics with humans. The tiny freshwater fish have a short life cycle, easily studied in the laboratory. The transparent embryos develop rapidly outside the mother's body. It transitions from a single cell into a free-swimming animal in just a few days.

With the many recent advances in the study of genetics and molecular biology, both the human and zebrafish genome sequences are completely known, said Tanguay.

"Science has learned that human and zebrafish genes are quite similar," said Tanguay. "We are thinking, if zebrafish and humans have the same genes, how is it that zebrafish are able to regenerate complex tissues, while humans are not?" They believe that this new approach will help to answer that question and provide a path to human tissue regeneration.