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Cited by 115Pancreatic function and diabetesDiabetes and associated disordersOrgan Transplantation Techniques and Outcomes

Pancreatic islet cryopreservation by vitrification achieves high viability, function, recovery and clinical scalability for transplantation

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Zhan, Li, Rao, Joseph Sushil, Sethia, Nikhil, Slama, Michael Q., Han, Zonghu, Tobolt, Diane, Etheridge, Michael, Peterson, Quinn P. +3 more·2022·Nature Medicine
DOI 10.1038/s41591-022-01718-1PMC PMC9018423
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Abstract

Pancreatic islet transplantation can cure diabetes but requires accessible, high-quality islets in sufficient quantities. Cryopreservation could solve islet supply chain challenges by enabling quality-controlled banking and pooling of donor islets. Unfortunately, cryopreservation has not succeeded in this objective, as it must simultaneously provide high recovery, viability, function and scalability. Here, we achieve this goal in mouse, porcine, human and human stem cell (SC)-derived beta cell (SC-beta) islets by comprehensive optimization of cryoprotectant agent (CPA) composition, CPA loading and unloading conditions and methods for vitrification and rewarming (VR). Post-VR islet viability, relative to control, was 90.5% for mouse, 92.1% for SC-beta, 87.2% for porcine and 87.4% for human islets, and it remained unchanged for at least 9 months of cryogenic storage. VR islets had normal macroscopic, microscopic, and ultrastructural morphology. Mitochondrial membrane potential and adenosine triphosphate (ATP) levels were slightly reduced, but all other measures of cellular respiration, including oxygen consumption rate (OCR) to produce ATP, were unchanged. VR islets had normal glucose-stimulated insulin secretion (GSIS) function in vitro and in vivo. Porcine and SC-beta islets made insulin in xenotransplant models, and mouse islets tested in a marginal mass syngeneic transplant model cured diabetes in 92% of recipients within 24–48 h after transplant. Excellent glycemic control was seen for 150 days. Finally, our approach processed 2,500 islets with >95% islets recovery at >89% post-thaw viability and can readily be scaled up for higher throughput. These results suggest that cryopreservation can now be used to supply needed islets for improved transplantation outcomes that cure diabetes.

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References 52 · Cited by 115

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Authors
Zhan, L., Rao, J. S., Sethia, N., Slama, M. Q., Han, Z., Tobolt, D., Etheridge, M., Peterson, Q. P., Dutcher, C. S., Bischof, J. C., & Finger, E. B.
Affiliations
  • University of Minnesota (US)
  • Mayo Clinic (US)
Corresponding author
Finger, Erik B.
ORCID
Venue
Nature Medicine
Publisher
Springer Science and Business Media LLC
Published
2022-03-14
Volume
28
Issue
4
Pages
798-808
ISSN
  • 1078-8956 (ISSN-L)
  • 1546-170X
DOI
10.1038/s41591-022-01718-1
PMC
PMC9018423
OpenAlex
W4221023904
Cited by
115
References
52
Citations by year
2026: 26 · 2025: 28 · 2024: 27 · 2023: 18 · 2022: 16
FWCI
21.27
Type
journal article
Language
en
Open access
Licence
Locations
  • Nature Medicine (publishedVersion, cc-by)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
Funders
  • National Science Foundation (R01HL135046, 1941543)
  • University of Minnesota
  • Regenerative Medicine Minnesota
  • Khalifa Bin Zayed Al Nahyan Foundation
  • National Institutes of Health (EEC 1941543)
  • Clinical and Translational Science Institute, University of Minnesota
  • National Heart, Lung, and Blood Institute (R01HL135046)
  • National Institute of Diabetes and Digestive and Kidney Diseases (R01DK131209, R01DK117425)
Topics
  • Health Sciences › Medicine › Surgery › Pancreatic function and diabetes
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Diabetes and associated disorders
  • Health Sciences › Medicine › Surgery › Organ Transplantation Techniques and Outcomes
Keywords
vitrification, islet transplantation, diabetes cure, rewarming, islet viability, stem cell-derived beta cells, porcine islets, human islets, glucose-stimulated insulin secretion, xenotransplantation
MeSH terms
Adenosine Triphosphate, Animals, Cryoprotective Agents, Diabetes Mellitus, Insulin, Islets of Langerhans, Swine, Cryopreservation, Islets of Langerhans Transplantation, Mice, Vitrification

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