Miller cells

Image of the brain’s myelin-forming cells, oligodendrocytes, that have been generated from neural stem cells in culture. (Image provided by the Freda Miller lab.)

Human endogenous repair – the ability of the body to repair itself – is a promising area of regenerative medicine therapy. Stem cells are at the heart of this process: they can repair tissues and organs damaged by acute injury, genetic disease or the aging process.

But how do researchers persuade stem cells in the brain to do that on demand? That is the question a team of interdisciplinary researchers at U of T and its affiliated hospitals is tackling, led by neuroscientist Freda Miller, formerly a senior scientist at The Hospital for Sick Children and now a professor at the University of British Columbia.

Miller is a stem cell biologist who focuses on the mechanisms of neural stem cell genesis and growth.

Freda Miller

Freda Miller

The team’s approach is to use advanced methods in the areas of stem cell biology, computational biology, physics, bioengineering and clinical work to identify promising drugs and regenerative molecules with the potential to stimulate repair activity.

The cutting-edge computational techniques the team uses are led by Gary Bader, one of the researchers on the project, and a professor of molecular genetics whose lab is located at the Donnelly Centre for Cellular and Biomolecular Research, U of T.

“We are developing artificial intelligence methods to understand how to activate and control tissue repair processes,” says Bader.

Bader lab modelling image

A deep learning model for changing cell fate using gene manipulation. (Image by Mehrshad Sadria, Bader lab.)

By combining the researcher’s specialties, the team combines data and computer modelling to look at individual stem cells in the brain and predict their behaviours. Through experimentation, they test if the cells behave the way they predicted. From there, the team casts a wide net, testing various ways to try to control cells’ behaviour with the end goal of convincing the stem cells to turn into cells that aid in healing and repair.

Gary Bader

Gary Bader

One of the areas the team has focused on is the generation of myelin, a substance that coats nerves and aids nerve impulse transmission. By repairing damaged or lost myelin, they aim to alleviate and potentially reverse the effects of diseases such as multiple sclerosis and brain injuries.

One finding that has emerged from this team is the application of Metformin, a common diabetes drug, to recruit stem cells for myelin repair. Through their studies, they have found Metformin may hold promise in treating children who have undergone brain radiation and people with brain or spinal cord injury. A new Metformin study that initiates a pilot clinical trial for Metformin in select children who have had an episode of multiple sclerosis is currently underway.

Back to “Five ways Medicine by Design is transforming the treatment of brain diseases.”