Engineers and medical researchers at the University of Minnesota Twin Cities and the Mayo Clinic have devised a new method for storing and rewarming specialized pancreatic islet cells at extremely low temperatures, potentially allowing for on-demand islet transplantation. The breakthrough in cryopreservation is a significant step toward a diabetic cure.
Diabetes is the seventh greatest cause of death in the United States, accounting for approximately 90,000 fatalities each year, according to the Centers for Disease Control and Prevention. While diabetes care has vastly improved in the 100 years after the discovery of insulin, even the most advanced treatments are still considered treatments rather than cures.
Diabetes mellitus, or diabetes, is a metabolic condition characterized by excessive blood sugar levels. Diabetic retinopathy, kidney failure, heart attacks, strokes, and lower limb amputation are all common complications of diabetes. Uncontrolled diabetes causes hyperglycemia, or high blood sugar, which causes catastrophic damage to many of the body’s systems, including the neurons and blood vessels, over time.
One option being investigated to cure diabetes is pancreatic islet cell transplantation, which involves doctors taking groups of cells from a healthy pancreas and transferring them to a recipient, who subsequently begins to generate and release insulin on their own.
One of the major drawbacks of this method is that single-donor transplants are sometimes insufficient to achieve insulin independence in the recipient. Two, three, or more donor islet infusions are frequently necessary, which increases the hazards associated with multiple surgical operations and significant immunosuppressive induction.
Pooling islets from several donors to achieve high islet dosage with a single infusion is one technique for solving the donor supply challenge. The inability to securely keep islets for lengthy periods of time limits this process. According to previous study, storage should be limited to 48 to 72 hours before to transplantation.
University of Minnesota researchers have devised a new method of islet cryopreservation that tackles the storage dilemma by allowing for quality-controlled, long-term preservation of islet cells that may be pooled and used for transplantation, according to new research published in Nature Medicine.
John Bischof, PhD, Distinguished McKnight University Professor of mechanical engineering and director of the University’s Institute for Engineering in Medicine, and Erik Finger, MD, PhD, associate professor of surgery at the University of Minnesota Medical School, M Health Fairview, led the research.
Our work provides the first islet cryopreservation protocol that simultaneously achieves high viability and function in a clinically scalable protocol. This method could revolutionize the supply chain for islet isolation, allocation, and storage before transplant. Through pooling cryopreserved islets prior to transplant from multiple pancreases, the method will not only cure more patients, but also make better use of the precious gift of donor pancreases.
Professor John Bischof
Both Bischof and Finger are a part of the National Science Foundation Engineering Research Center for Advanced Technologies for the Preservation of Biological Systems (ATP-Bio) and co-direct the Center for Organ Preservation at the University of Minnesota.
Preventing or delaying the onset of type 2 diabetes can be accomplished through a nutritious diet, frequent physical activity, maintaining a healthy body weight, and avoiding tobacco use. Diet, physical activity, medication, and regular screening and treatment for complications can all help to treat diabetes and delay or prevent its repercussions.
The study found:
- Excess cryoprotective fluid was evacuated using a customized cryomesh system, allowing for rapid cooling and rewarming on the order of tens of thousands of degrees per second while avoiding problematic ice formation and lowering toxicity.
- Even after nine months of storage, this new cryopreservation approach revealed high cell survival and functionality (90 percent for mouse islet cells and roughly 87 percent for pig and human islet cells). The theoretical storage time with this prospective cryopreservation method is limitless.
- The transplantation of these cryopreserved islet cells into mice healed diabetes in 92 percent of recipients within 24 to 48 hours.
- These findings show that this new cryopreservation approach could be a significant tool for enhancing the islet supply chain by allowing islets from numerous pancreases to be pooled and thereby boosting diabetes-curing transplantation outcomes.
“Our work provides the first islet cryopreservation protocol that simultaneously achieves high viability and function in a clinically scalable protocol,” Bischof said. “This method could revolutionize the supply chain for islet isolation, allocation, and storage before transplant. Through pooling cryopreserved islets prior to transplant from multiple pancreases, the method will not only cure more patients, but also make better use of the precious gift of donor pancreases.”
The researchers also mentioned that this technology might be scaled up to reach vast numbers of patients suffering from this progressively severe disease all across the world. The World Health Organization (WHO) wants to encourage and support the adoption of effective diabetes surveillance, preventive, and control methods, particularly in low- and middle-income countries.
“This exciting development by our multidisciplinary research team brings engineering approaches to solve an important medical challenge the cure of diabetes,” said Finger. “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.”
In addition to Bischof and Finger, the research team included from the University of Minnesota co-first author postdoctoral fellows Li Zhan (mechanical engineering) and Joseph Sushil Rao (surgery).
Also part of the study team were Nikhil Sethia (chemical engineering and materials science), Zonghu Han (mechanical engineering), Diane Tobolt (surgery), Michael Etheridge (mechanical engineering), and Cari S. Dutcher (mechanical engineering; chemical engineering and materials science). Mayo Clinic researchers who were part of the team included Michael Q. Slama and Quinn P. Peterson.
Grants from Regenerative Medicine Minnesota, the National Science Foundation, and the National Institutes of Health helped fund this research. The Schulze Diabetes Institute at the University of Minnesota, the Division of Transplantation in the Department of Surgery, the Kuhrmeyer Chair in Mechanical Engineering, and the Bakken Chair in the Institute for Engineering in Medicine all contributed additional funds.
The J.W Kieckhefer Foundation, the Stephen and Barbara Slaggie Family, and the Khalifa Bin Zayed Al Nahyan Foundation all contributed to this research. The Characterization Facility at the University of Minnesota was employed in this study.
