Researchers at McGill University and the Research Institute of the McGill University Health Center (RI-MUHC) have developed a novel device to transplant insulin-producing cells that integrates directly with existing blood vessels in the body. The technology, which showed promising results in preclinical trials, aims to overcome key challenges of emerging long-term cell-based treatments for Type 1 diabetes. As well as serving as an artificial pancreas, it potentially could be used to replace or support the function of other organs.
Unlike previous experimental implants, the device is designed to provide immediate blood supply while still creating a barrier against immune rejection, the research team said.
"Insulin, discovered in Canada 100 years ago, has saved many lives, but it's not a cure," said Corinne Hoesli, study co-author and Associate Professor in the Department of Chemical Engineering. "We designed a device with a pre-formed network of artificial blood vessels that looks like a vascular bypass graft, except we introduced insulin-secreting cells into it."
"This starts to look like a bona fide artificial organ," she said, adding that a key element of success was interdisciplinary collaboration with researchers across Canada, including teams from Université Laval, the University of British Columbia, and Université de Montréal.
Reducing the burden on patients
Normally, the pancreas regulates blood sugar levels. It releases insulin to lower glucose and glucagon to raise it. For the 9.5 million people worldwide who live with Type 1 diabetes, this process is interrupted: the pancreas stops producing enough insulin, causing glucose and ketones to build up in the blood. Many also experience severe hypoglycemic episodes - when administering too much insulin can become life-threatening. In Canada, the lifespan of people with Type 1 diabetes is reduced by around 10 years.
Instead of synthetic insulin administration, another clinical approach is to transplant insulin-producing cells found in pancreatic islets of Langerhans. Islet transplantation using cells from deceased human donors is an approved therapy in Canada. Very few people are treated each year because of limited donor organ supply and the need for lifelong immunosuppression medication to avoid graft rejection. Additionally, more than half of the transplanted cells die shortly after transplantation because of a lack of immediate blood supply.
This new device is designed to overcome these challenges: it uses cells that can be grown in large numbers in the lab and creates a protective barrier (encapsulation) to deflect the immune system.
To support the number of insulin-secreting cells required for the device to work effectively, the researchers used 3D printing and repeated coating strategies to create multiple parallel blood channels. These channels nourish the graft and help ensure insulin can be delivered efficiently throughout the body as soon as blood flow is established.
Looking ahead
The researchers said a key feature of the device is its adaptability.
"We could make it in the lab, sterilize it, and ship it anywhere in the world for clinical teams to infuse with relevant therapeutic cells," Hoesli said.
Beyond diabetes, the device could also be used to test different blood vessel structures and branching patterns, as well as different cell types, helping to advance preclinical testing for other artificial organs.
About this study
"Multi-compartment Bioartificial Organs Engineered via Iterative Sacrificial 3D Printing and Vascular Integration," by Jonathan A. Brassard, Saleth Sidharthan Dharmaraj, Hamid Ebrahimi Orimi, Si Da Ling, Daria Vdovenko, Yannick Rioux, Hanwen Wang, Marc-Antoine Campeau, Kurtis Champion, Florent Lemaire, Brenden N. Moeun, Jia Zhao, Shenghui Liang, Timothy J. Kieffer, Jean I. Tchervenkov, Gilles Soulez, André Bégin-Drolet, Jean Ruel, Richard L. Leask, Steven Paraskevas and Corinne A. Hoesli, was published in Cell Biomaterials.
Key funders of this study include the Canadian Institutes of Health Research, Breakthrough Type 1 Diabetes (formerly JDRF), the Natural Sciences and Engineering Research Council of Canada, the Canadian Stem Cell Network and the Quebec Network for Cell, Tissue and Gene Therapy - ThéCell, a thematic network supported by the Fonds de recherche du Québec-Santé.
