As is often the case in science, a remarkable discovery by Monash University’s regenerative medicine experts happened completely by accident. Or, more accurately, it was a discovery born from a mistake.
Researchers at ARMI, the University’s Australian Regenerative Medicine Institute, were looking into unanswered questions regarding how muscle cells respond to stem cells when the muscle is damaged. The point of this was to figure out a way of getting muscle to better regenerate, or rebuild itself.
The ARMI team was led by then PhD student Dr Dhanushika Ratnayake and ARMI’s director of research, Professor Peter Currie. They had been making images and “home movies” of goings-on inside the larvae of the institute’s zebrafish larvae, the go-to tool for studying regeneration, because the tiny baby fish are incredibly adept at rebuilding themselves.
“One of these movies,” says Professor Currie, “captured a bizarre behaviour where the muscle cells came out to guide the stem cells back to where the hole was, the wound.”
He was convinced this was due to the actions of a macrophage, a type of cell that helps the immune system. But he was mistaken.
“Danni proved within a month that the boss was completely wrong,” he says.
A medical science breakthrough
The answer was with the macrophages – but it was something new to medical science.
The landmark project of experiments – over five years – is published in Nature journal this week, with collaborators from the Netherlands, France, Germany, the University of Melbourne, and the Walter and Eliza Hall Institute of Medical Research (WEHI).
At ARMI, Associate Professor Mikael Martino and Professor Graham Lieschke’s linked labs worked closely on the project.
Dr Ratnayake is lead author. She takes up the story.
“We saw that these particular macrophages, or immune cells, came to the injury site and then, to our surprise, hung around,” she says. “We thought they came in and cleaned up the mess and left; we thought that was their role.
“But we saw some stayed with the stem cells, and had very intimate associations with the stem cells, always in contact. We saw that this subset of macrophages are the ones that make the muscle stem cells proliferate, and this proliferation is essential for them to make new muscle fibre.”
