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Dr Brian Ballios is pictured with a mouse in his lab at The University of Toronto on Thursday May 14, 2015. (Chris Young For The Globe and Mail)
Dr Brian Ballios is pictured with a mouse in his lab at The University of Toronto on Thursday May 14, 2015. (Chris Young For The Globe and Mail)

Injectable gel makes inroads against blindness and stroke Add to ...

Brian Ballios still remembers the moment, 18 months ago, when he was staring at a monitor in a darkened room at the University of Toronto watching a closeup of a mouse’s eye that he had injected with retinal cells grown from stem cells in his lab.

The mouse was born blind – genetically engineered so that its retina could not respond to light. But when a light flashed in the lab, the mouse’s pupil contracted.

“That was thrilling,” Dr. Ballios said. “It showed not only that the cells were functioning, but that they were sending signals back to the brain.”

The result, described Thursday in the journal Stem Cells Reports, is the latest evidence that a method developed by researchers at U of T can be used to surmount one of the most challenging problems in regenerative medicine: getting replacement cells to where they are needed in the body and keeping them there long enough to restore function to damaged or deficient tissues.

The study details two applications of the method in mice. Dr. Ballios worked with retinas while Michael Cooke, a postdoctoral researcher, treated brain tissue that was damaged in a manner that mimics the effects of stroke. Both saw positive results. Researchers say the method developed by the U of T group has the potential to be used more widely in stem-cell therapy.

“This is a cell-delivery vehicle that could be used essentially for anything,” said Derek van der Kooy, a neurobiologist who co-leads the effort with bio-engineer Molly Shoichet.

A key part of the research is a multipurpose material known as a hydrogel whose properties can be tailored to change with its setting. The hydrogel flows like water through a syringe, carrying cells with it. But once it’s warmed to body temperature it stiffens and provides a scaffolding that helps keep implanted cells from clumping up or drifting away. The new work shows the hydrogel also interacts with the cells, helping keep them alive so that they can gradually integrate into the retina.

The work comes as several clinical trials have begun or are poised to begin around the world to deploy stem cells in human patients – a long anticipated return on decades of research as scientists have gradually learned to work with the unspecialized cells and program them to take on a multitude of roles.

The eye has been the proving ground for much of the stem cell work now heading for the clinic. Stem cells have the potential to restore sight for those suffering from conditions such a macular degeneration or retinitis pigmentosa – both of which involve a loss of light-sensing cells in the retina.

The barrier is how to get cells to the retina where they can be integrated. Methods for implanting stem cells include placing them on a plastic sheet that is surgically implanted. The U of T group’s hydrogel is an attractive alternative because it is far less invasive, yet it manages to keep the cells in place.

“Everybody knows it’s better to use a syringe rather than forceps for eye surgery. Retinal surgeons are comfortable with that type of approach,” said Michael Young, a developmental neurobiologist at Harvard University and the Schepens Eye Research Institute in Boston.

Dr. Young, who was not involved with the U of T study, said the group’s method was a significant step forward.

Although the results show a big improvement relative to earlier efforts by the same team, the method is far from optimized. In the best cases only 8 to 9 per cent of the injected cells managed to hook up to the retina where they conferred a limited ability to perceive light.

“We’re getting hundreds of cells integrating, which gives us some response, but ideally we’d want to get tens of thousands of cells integrating,” Dr. Ballios said.

Nevertheless, he added, there is clear potential for human treatment.

“I see patients in my clinic on a regular basis who have very low vision … This is essentially the analogous situation. And seeing that the cells we transplanted are communicating with the brain and sending back signals is very exciting. These are big jumps in the field.”

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