New method of pancreatic islet cryopreservation marks breakthrough for diabetes cure
Date:
March 23, 2022
Source:
University of Minnesota
Summary:
Engineering and medical researchers have developed a new process
for successfully storing specialized pancreatic islet cells at
very low temperatures and rewarming them, enabling the potential
for on-demand islet transplantation. The breakthrough discovery
in cryopreservation is a major step forward in a cure for diabetes.
FULL STORY ========================================================================== 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, 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. While diabetes management has improved
greatly over the 100 years since the discovery of insulin, even the most
modern methods remain a treatment for the condition rather than a cure.
Pancreatic islet cell transplantation -- a process where doctors take
groups of cells from a healthy pancreas and transfer them to a recipient,
which then begin to make and release insulin on their own -- is one method being explored to cure diabetes. One of the main limitations 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.
One strategy for overcoming the donor supply problem is to pool islets
from multiple donors, achieving high islet dosage with a single
infusion. 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.
In new research published in Nature Medicine, University of Minnesota researchers have developed 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.
The study was led by John Bischof, PhD, a mechanical engineering
Distinguished McKnight University Professor and director of the
University's Institute for Engineering in Medicine, and Erik Finger,
MD, PhD, associate professor of surgery in the University of Minnesota
Medical School, M Health Fairview. 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.
==========================================================================
The study found:
* By using a specialized cryomesh system, excess cryoprotective
fluid was
removed, which allowed rapid cooling and rewarming on the order of
tens of thousands of degrees per second while avoiding problematic
ice formation and minimizing toxicity.
* This new cryopreservation method demonstrated 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.
* In mice, the transplantation of these cryopreserved islet cells
cured
diabetes in 92% of recipients within 24 to 48 hours after
transplant.
* These 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," 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 pointed out that this method has the ability to
be scaled up to reach large numbers of people worldwide who suffer from
this progressively debilitating disease.
"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.
This work was supported by grants from Regenerative Medicine Minnesota,
the National Science Foundation, and the National Institutes of
Health. Additional funding was provided by the University of Minnesota's Schulze Diabetes Institute, the Division of Transplantation at the
Department of Surgery, Kuhrmeyer Chair in Mechanical Engineering,
and the Bakken Chair in the Institute for Engineering in Medicine. The researchers also acknowledge the J.W Kieckhefer Foundation, the Stephen
and Barbara Slaggie Family, and the Khalifa Bin Zayed Al Nahyan Foundation
for supporting this work. The University of Minnesota's Characterization Facility was used in this research.
Video:
https://youtu.be/VoLyLgT9Tuc
========================================================================== Story Source: Materials provided by University_of_Minnesota. Note:
Content may be edited for style and length.
========================================================================== Journal Reference:
1. Li Zhan, Joseph Sushil Rao, Nikhil Sethia, Michael Q. Slama,
Zonghu Han,
Diane Tobolt, Michael Etheridge, Quinn P. Peterson, Cari S. Dutcher,
John C. Bischof, Erik B. Finger. Pancreatic islet cryopreservation
by vitrification achieves high viability, function, recovery and
clinical scalability for transplantation. Nature Medicine, 2022;
DOI: 10.1038/ s41591-022-01718-1 ==========================================================================
Link to news story:
https://www.sciencedaily.com/releases/2022/03/220323114518.htm
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