Stem cell transplants treat blindness in mini pigs

Scientists at Université de Montréal (UdeM) have successfully transplanted retinas made from stem cells into blind mini pigs, apparently restoring their vision in the process. Described in the journal Development, the research shows potential for treating retinal degenerative diseases in humans.

In most cases, loss of vision is caused by damage to the macula, a region in the centre of the retina. The macula is rich in cone photoreceptors — cells important for perceiving colour and seeing finer details. There are currently no approved treatments to replace the damaged macula, but that hasn’t stopped researchers from trying.

In their stem cell and developmental biology laboratory of the UdeM-affiliated Maisonneuve-Rosemont Hospital, Professor Gilbert Bernier and his team developed a method to coax stem cells into forming sheets of cells that recapitulate the structure of the human retina. The type of stem cells they used are called human induced pluripotent stem cells — immature cells ‘reprogrammed’ from an adult (mature) cell that can differentiate into any type of cells in the body. Using the stem cells, the researchers made ‘retinal sheets’ that are enriched in immature versions of the cone photoreceptor cells, which could become mature cone cells when cultured in the lab.

“Some approaches [to macula repair] use dissociated photoreceptor cells; others create micro-dissected retinal organoids, which are lab-grown ‘mini organs’ in a dish,” Bernier said. “In contrast, our method allows the spontaneous formation of a flat retinal tissue that is already polarised and organised, as in the human embryonic retina.”

After successfully creating the retinal sheets in a dish, the researchers tackled the next challenge: transplanting these sheets into mini pigs with damaged macula. Once that was done, they found that the retinal grafts were able to integrate into each pig’s damaged retinal tissue.

“To get as close as possible to human clinical application, we chose mini pigs because the size of their eyes is near that of humans and the animals are about the same weight as humans,” Bernier explained.

The mini pigs ended up showing signs of restored vision: new neural connections were formed between the grafted photoreceptor cells and the pigs’ neural cells, and the scientists could detect neural activity of the photoreceptors at the grafted area when the mini pigs were placed in a well-lit room.

A limitation of this method lies in the difficulty of controlling the placement and orientation of the grafts during surgery, as the macula is only 4 mm in diameter — about the length of a grain of rice.

“To properly orient, place and stabilise the graft in the retina remains a big surgical challenge,” Bernier said. His team are now working to improve the transplantation success rate, validating an experimental retinal surgery device to ensure proper orientation and implantation of the graft at the correct retinal disease site.

Image credit: iStock.com/GlobalP