Engineering and medical researchers at the University of Minnesota Twin Cities and Mayo Clinic have developed a new process for successfully storing specialized pancreatic islet cells at very low temperatures and rewarming them with a laser and gold nanoparticles, enabling the potential for on-demand islet transplantation. The breakthrough discovery in cryopreservation is a major step forward in a cure for diabetes. 

According to the Centers for Disease Control and Prevention, diabetes is the seventh leading cause of death in the United States, accounting for nearly 90,000 deaths each year. Despite 100 years of therapeutic development since the discovery of insulin, current diabetes therapies, such as continuous glucose monitors, insulin pumps and closed-loop systems, remain a treatment for the condition rather than a cure of the disease. 

Pancreatic islet cell transplantation, a process where doctors take groups of cells from a healthy pancreas and transfer them to a recipient who then begins to make and release insulin on their own, is one method being explored to cure diabetes. However, a limitation of this approach is that transplants from a single donor are often insufficient to achieve insulin independence in the recipient. Frequently, two, three or more donor-islet infusions are required, which adds risks associated with repeated surgical interventions and multiple rounds of strong immunosuppression induction. 

A common strategy for overcoming the donor supply problem is to pool islets from multiple donors, achieving high islet dosage with a single infusion, but this process is limited by the inability to safely store islets for long periods of time. Previous research has shown storage to be limited to 48 to 72 hours before transplantation. While some groups have shown the feasibility of culturing islets for extended periods (weeks to months), the majority have reported reduced islet recovery and loss of endocrine function over time. 

The breakthrough from the research done by the University of Minnesota Twin Cities and Mayo Clinic provides a new method of islet cryopreservation that solves the storage problem by enabling quality-controlled, long-term preservation of the islet cells that can be pooled and used for transplant. 

By using a specialized cryomesh system, excess cryoprotective fluid is removed, which allows rapid cooling and rewarming on the order of tens of thousands of degrees per second while avoiding problematic ice formation and minimizing toxicity. The new cryopreservation method demonstrates high cell survival rates and functionality (90% for mouse islet cells and about 87% for pig and human islet cells), even after nine months of storage. Storage with this potential cryopreservation approach is theoretically indefinite. Furthermore, in mice, the transplantation of these cryopreserved islet cells cured diabetes in 92% of recipients within 24 to 48 hours after transplant. The results suggest that this new cryopreservation protocol may be a powerful means of improving the islet supply chain, allowing pooling of islets from multiple pancreases, and thereby improving transplantation outcomes that can cure diabetes. 

“Our work provides the first islet cryopreservation protocol that simultaneously achieves high viability and function in a clinically scalable protocol,” said John Bischof, Ph.D., a Distinguished McKnight University Professor in mechanical engineering and director of the University of Minnesota's Institute for Engineering in Medicine. “This method could revolutionize the supply chain for islet isolation, allocation and storage before transplant. By pooling cryopreserved islets before transplant from multiple pancreases, the method will not only cure more patients, but also make better use of the precious gift of donor pancreases.” 

Researchers also pointed out that this method can be scaled up to reach large numbers of people worldwide who suffer from this progressively debilitating disease. “Despite decades of research, islet transplantation has remained just around the corner; ever with great promise, but never quite within reach. Our technique for cryopreserving islets for transplantation could be a significant step towards finally achieving that lofty goal,” said Erik Finger, MD, Ph.D., associate professor of surgery at the University of Minnesota Medical School, M Health Fairview.

This research is part of a larger effort involving cryopreservation methods led by the University of Minnesota. In 2020, the University of Minnesota and Massachusetts General Hospital were awarded $26 million over five years from the National Science Foundation to create the Engineering Research Center for Advanced Technologies for the Preservation of Biological Systems (ATP-Bio). ATP-Bio aims to achieve major bioengineering breakthroughs by developing and deploying the technology to “stop biological time” through temperature control – that is, to “bio-preserve” or “cryopreserve” numerous biological systems. ATP-Bio includes 30 senior personnel from seven institutions across the US and Canada.

Image: University of Minnesota College of Science and Engineering Professor John Bischof and mechanical engineering Ph.D. student Lakshya Gangwar use one-of-a-kind pieces of equipment to cryopreserve and rewarm cells, tissues and even entire organs. Credit: Rebecca Slater