New CIHR/JDRF Teams Grant Led by Dr. Cristina Nostro

September 7, 2021
By Krista Lamb

photo of Cristina Nostro

In December 2020, CIHR and JDRF Canada announced the winners for a new teams grant program, which aims to accelerate the clinical translation of universal donor stem cell-derived islet cells for the treatment of type 1 diabetes. BBDC member, Dr. Cristina Nostro, who is an associate professor in U of T’s Department of Physiology and a Senior Scientist at the McEwen Stem Cell Institute at University Health Network, was named as Principal Investigator on one of these five-year grants.

The project, which was funded as part of JDRF Canada’s Partnership to Defeat Diabetes and CIHR’s 100 Years of Insulin: Accelerating Canadian Discoveries to Defeat Diabetes programs, is titled “Using novel transplantation strategies and HLA-edited hypoimmunogenic hPSCs to develop a superior islet-like product for T1D treatment.”

Nostro, originally from Italy, trained under Dr. Gordon Keller and has become a leading expert on the development of insulin-producing cells using stem cells. For this grant, she has put together an exceptional team of scientists who will collaborate across disciplines on the project.

“We were extremely excited that the Government of Canada and JDRF decided to create this wonderful opportunity for us to team up with our colleagues from around the country to develop the program,” says Nostro.

Her lab has been working with a cell line that was generated by Dr. David Russell at the University of Washington, Seattle, who knocked out genes that would prevent the expression of HLA (human leukocyte antigens – a protein) on the surface of the cell lines. This cell line, in theory, could be used without immunosuppression drugs, because it would be invisible to the immune system. These drugs can be harsh and have multiple side effects, which has meant that current treatments, like pancreas and islet transplants, could only be considered for the most pressing cases.

“The hope is that in the future we would have a product that could be transplanted in the absence of immunosuppression. That would mean people with type 1 diabetes don’t need to take this drug,” Nostro says. The downside of immunosuppression is that it can be really harsh and increase the risk of tumors. “Ultimately, if you can eliminate immunosuppression, then you could offer stem-cell-derived islets to more people living with diabetes, maybe even children, and hopefully eliminate the need for insulin injections”.

Nostro’s collaborators on this grant are some of Canada’s leading diabetes researchers, including Dr. Daniel Drucker from the Lunenfeld Tanenbaum Research Institute in Toronto, Dr. Sara Vasconcelos from the Toronto General Hospital Research Institute, and Drs. Greg Korbutt and Andrew Pepper from the University of Alberta. Each of them manages a different area of the project.

The stem cell-derived islets Nostro creates in her lab will be tested for functionality to ensure that they are as good as primary islets. Additionally the team will test their immunogenicity and implement novel transplantation approaches to optimize the transplant site and provide an environment where islets can thrive.

“The goal of our project is to make a product that is better than human islets. Islet transplantation is inherently variable as every batch of islets, because it comes from a different person, it has inheritable traits and variability. You could have one islet preparation that is functioning very well, another islet preparation might not be that good. And with human-derived islets we expect to have something that is always consistent because it’s batch tested,” Nostro explains of the difference when making cells in the lab.

The teams grant aspect of this project really appeals to Nostro, who is committed to collaborative work that moves things forward more quickly for people living with diabetes. “You can do a lot of things in your lab, but if you have a big project that is going to potentially affect the life of patients, you need to work with as many experts as possible. Because of this funding competition, I have had the possibility to dream big and assemble an elite group of scientists with expertise in vascular biology, islet transplantation, immunology and beta cell biology to focus on addressing all of the current challenges preventing cell therapy from becoming the first line of treatment for patients living with diabetes,” she says. “You can’t do everything by yourself, you need to build this network of collaborators.”

Read more about this project.