Stem cell-derived photoreceptor cells were injected into the retina (pictured), leading to improved eyesight. The U of T research group has created a new biogel which enabled vast improvement in stem cell survival, distribution and results in blindness and stroke partial recovery

Stem cell-derived photoreceptor cells were injected into the retina (pictured), leading to improved eyesight. The U of T research group has created a new biogel which enabled vast improvement in stem cell survival, distribution and results in partial recovery of blindness and stroke.
Photo Credit: UofT Engineering

Reversing blindness and stroke: new Canadian research

New research has led to a major advance in the eventual treatment for blindness and for repairing brain damage from stroke.

Using stem cells and a newly invented biogel delivery medium, the researchers have shown greatly improved results in restoring vision and motor control in test mice.

Molly Shoichet (PhD, ChemE) co-supervised the research. She is a professor in chemical engineering and applied chemistry at the University of Toronto.

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Professor Molly Shoichet (PhD, ChemE) U of T professor and co-supervisor of the research teams She and M Cooke are co-inventors of the new biogel technology
Professor Molly Shoichet (PhD, ChemE) U of T professor and co-supervisor of the research teams. She and M Cooke are co-inventors of the new biogel technology © Roberta Baker- U of T

The researchers in Toronto have created a new biogel (hydrogel) delivery medium which provides several advantages in medical applications involving stem cells.

Stem cells are basic cells which can evolve into several different specific cells in the body.

Professor Shoichet notes that while in recent times great advances  have been made in using stem cells in medicine, the survival rate of the cells is very low.  She says for these cells to work, ie evolve into the specific cells needed to repair damage to specific organs etc, they have to survive long enough to integrate and adapt into the body system, and typically only about 4-5 percent of the stem cells survive.

With their new biogel innovation, including hyaluronan and methylcellulose,  the survival rate of the stem cells has doubled.  As she says, this means that the medical effectiveness of the treatment is also doubled which is a huge advance.

This newly created biogel also has a distinct advantage over conventional saline as it distributes itself more widely into the region needed as opposed to simply remaining as an injected blob near the injection site which was the case with previous technology.

“After cell transplantation, our measurements showed that mice with previously no visual function regained approximately 15% of their pupillary response. Their eyes are beginning to detect light and respond appropriately,” says Brian Ballios who led this phase of research.

Neural stem cells (fluorescently green) in the hydrogel (HAMC – hyaluronan/methylcellulose) in a model stroke-injured mouse brain – this figure demonstrates a lovely distribution of cells in the brain and great survival of those cells – this led to improved motor function back to baseline levels pre-injury.
Neural stem cells (fluorescently green) in the hydrogel (HAMC – hyaluronan/methylcellulose) in a model stroke-injured mouse brain – this figure demonstrates a lovely distribution of cells in the brain and great survival of those cells – this led to improved motor function back to baseline levels pre-injury. © Shoicet et al -U of T

To create the new gel, they were seeking to achieve several of their criteria; it had to be deliverable through an ultra fine needle, gel upon delivery, be compatible with the body, and dissipate safely soon after. They soon found it also greatly improved cell survival as well.

A more detailed image in the
A more detailed image in the “stroke” mouse brain. The transplanted cells are seen in green and the host neurons in red. The cells were transplanted 4 days after stroke injury and the image was captured 4 weeks post transplantation. The transplanted cells can be seen to be putting out processes into the host tissue (these are the thin string-like green lines). © U of T Engineering

Video of the new biogel with penny for size comparison

In terms of the process involving retinal repair, the Canadian team also may be the only ones using direct injection as opposed to other current forms of research requiring a much more complicated surgical process involving growing retinal cells on a flat sheet and inserting that into the eye.

After transplantation into blind mouse eyes in a hydrogel delivery vehicle, retinal stem cell (RSC)-derived photoreceptors (green) integrate amongst the cells of the host retina (cells shown in blue), and extend light sensitive processes (red), which help to regenerate lost vision.
After transplantation into blind mouse eyes in a hydrogel delivery vehicle, retinal stem cell (RSC)-derived photoreceptors (green) integrate amongst the cells of the host retina (cells shown in blue), and extend light sensitive processes (red), which help to regenerate lost vision.” © UofT Engineering

Professor Shoichet points out that their innovation has also shown real progress in treating a completely different injury with completely different cells, that of stroke.

Postdoctoral fellow Michael Cooke who worked on this phase said that within weeks of injection into the brains of “stroke-mice”, they were seeing significant improvement in motor coordination of the subjects.

Professor Shoichet says, the research team is now working on improvements to the hydrogel to enable further increase in cell survival but notes that this innovation, while certainly not eliminating blindness, nor stroke, is a major step forward.

The team is also excited about the fact that this opens the door to an even wider variety of applications in research, and eventually clinical medicine.

The scientists and engineers behind the breakthrough (L-R): Molly Shoichet, Derek van der Kooy, Michael Cooke, Cindi Morshead and Brian Ballios
The scientists and engineers behind the breakthrough (L-R): Molly Shoichet, Derek van der Kooy, Michael Cooke, Cindi Morshead and Brian Ballios © Roberta Baker- U of T

Conducted through the U of T’s Donnelly Centre for Cellular and Biomolecular Research, their research was published in today’s issue of Stem Cell Reports, the official scientific journal of the International Society for Stem Cell Research. The research paper is entitled. “A Hyaluronan-Based Injectable Hydrogel Improves the Survival and Integration of Stem Cell Progeny following Transplantation”

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