November 02, 2022 Delving deep into cellular therapy

Who:

Dr. Corinne Hoesli, professor and head of the Stem Cell Bioprocessing Laboratory at McGill University

Research highlights/discoveries:

• Developing better therapeutic cell culture methods

• Improving islet transplantation using protective devices

• Using 3D printing to engineer an artificial pancreas

Dr. Corinne Hoesli at a glance:

• Awarded the Étoiles effervescence (Effervescence Stars) award from Montreal InVivo (2019)

• Appointed Canada Research Chair in Cellular Therapy Bioprocess Engineering (2014)

• Received the Martin Sinacore Outstanding Young Investigator Award from Engineering Conferences International & Biogen Idec Inc. (2014)

First off, can you briefly explain how islet transplants work for people with diabetes?

Islet transplantation is an alternative to insulin therapy. It involves taking cells from the pancreas of a deceased donor and implanting them into the liver of someone living with diabetes. In some cases, people who have this procedure can be off insulin for years. Even for those who need to go back on insulin a few years after the transplant, it typically becomes easier for them to manage their blood sugar (glucose) and avoid low blood sugar (hypoglycemia), which can be life-threatening.

In Canada, we are leaders in this technology, but we are limited by the number of potential islet donors. Also, the current therapy means transplant recipients need to take medication that suppresses their immune system for the rest of their lives, so their body won’t reject the transplant. That lifelong immune suppression increases their risk of infection and even cancer. Because of this, few patients are eligible for the therapy. To increase access, we ideally require an unlimited source of islets and a way to avoid the need for anti-rejection medications.

How did you get interested in diabetes research?

I did my undergraduate degree in biochemistry and chemical engineering. I became fascinated with stem cells after a lecture in one of my classes, but very few engineers worked on this topic at the time. I decided to purse graduate studies in the laboratory of James Piret at the University of British Columbia (UBC), who was starting up a project on diabetes.

That initial project didn’t pan out, but a side project took off that ended up making up most of my Ph.D. I developed a new method to encapsulate islets in protective beads—imagine caviar, but with insulin-producing cells inside the ‘eggs.’ At that time, key papers were published showing that insulin-producing cells could be obtained from stem cells—a virtually unlimited source of cells. It became even more imperative to find a way to transplant these cells safely, for example using encapsulation. The technology I had developed became even more relevant after those papers were published.

I met many people with type 1 diabetes during my studies, and I have a close friend who has maturity-onset diabetes of the young (MODY). Diabetes also runs in my family due to a rare mitochondrial mutation.

Tell us about your current research in diabetes.

As engineers, our goal is to work closely with doctors, as well as stem cell and islet biologists, to improve the most promising current therapies. We apply engineering thinking to every step of the islet biomanufacturing pipeline. For example, we can take a protocol developed in other laboratories and see how we can best scale it up—the same way you would take your mother’s soup recipe and find a way to make soup for a large group of people. We also design islet transplantation devices. We consider many criteria in our design strategy: for example, how nutrients will reach the islets, how insulin secreted by the islets will reach the bloodstream, and whether the device can protect the islets from rejection. We do this with methods like computer simulations, 3D printing and bioreactors for cell production.

For my project supported by Diabetes Canada, we are engineering a new vascularized device for islet transplantation. We are working closely with Steven Paraskevas (McGill University Health Centre), who leads the islet transplantation program in Quebec; Timothy Kieffer (UBC), with his expertise in stem cell differentiation and physiology; and Sylvie Lesage (Université de Montréal), who helps us better understand immune reactions to the transplants. Other collaborators include Cherie Stabler (University of Florida), Lauren Flynn (Western University), and Ignacio Anegon (Université de Nantes). Many trainees are the ones actually doing the work—including Florent Lemaire, Jonathan Brassard, and Brenden Moeun in our lab.

How do you hope your research will impact Canadians living with type 1 diabetes?

As an engineer, I’m excited to work with scientists and doctors to make cell therapy for diabetes a reality.

Now that we’ve found a reliable source to draw cells from, it’s critical to find the best way to efficiently manufacture and deliver them to people with diabetes. We also need to reduce costs, which could be prohibitive—especially in countries with publicly funded universal healthcare systems such as Canada. We have a significant head start in Canada, with many experts in islet transplantation and diabetes working together toward the same goal.

Another personal goal over the next five years is to establish better communication channels with those living with diabetes in Canada. If you’re interested in our research or islet transplantation in general, please reach out! 

The last word

“Dr. Hoesli’s innovative work advancing cellular therapy as a treatment for type 1 diabetes is a perfect example of what is possible when we invest in new, outside-the-box research and approaches,” says Laura Syron, president and CEO of Diabetes Canada. “That is why we are proud to have provided more than $140 million in research grants, awards, and partnerships to scientists across the country since 1975.”

Did you know?

In 2013, Debbie Sissmore, who has type 1 diabetes, was the 60th person in all of Canada to undergo an islet cell transplant. This November, which marks Diabetes Awareness Month across the globe, we can all take action (big or small) to End Diabetes. Help us fund research like that of Dr. Hoesli, which has the power to change lives. Donate now. #LetsEndDiabetes