Vitrification and Nanowarming of Kidneys

Anirudh Sharma, Joseph Sushil Rao, Zonghu Han, Lakshya Gangwar, Baterdene Namsrai, Zhe Gao, Hattie L. Ring, Elliott Magnuson, Michael Etheridge, Brian Wowk, Gregory M. Fahy, Michael Garwood, Erik B. Finger, John C. Bischof

Research output: Contribution to journalArticlepeer-review

Abstract

Vitrification can dramatically increase the storage of viable biomaterials in the cryogenic state for years. Unfortunately, vitrified systems ≥3 mL like large tissues and organs, cannot currently be rewarmed sufficiently rapidly or uniformly by convective approaches to avoid ice crystallization or cracking failures. A new volumetric rewarming technology entitled “nanowarming” addresses this problem by using radiofrequency excited iron oxide nanoparticles to rewarm vitrified systems rapidly and uniformly. Here, for the first time, successful recovery of a rat kidney from the vitrified state using nanowarming, is shown. First, kidneys are perfused via the renal artery with a cryoprotective cocktail (CPA) and silica-coated iron oxide nanoparticles (sIONPs). After cooling at −40 °C min−1 in a controlled rate freezer, microcomputed tomography (µCT) imaging is used to verify the distribution of the sIONPs and the vitrified state of the kidneys. By applying a radiofrequency field to excite the distributed sIONPs, the vitrified kidneys are nanowarmed at a mean rate of 63.7 °C min−1. Experiments and modeling show the avoidance of both ice crystallization and cracking during these processes. Histology and confocal imaging show that nanowarmed kidneys are dramatically better than convective rewarming controls. This work suggests that kidney nanowarming holds tremendous promise for transplantation.

Original languageEnglish (US)
JournalAdvanced Science
Volume8
Issue number19
Early online dateAug 11 2021
DOIs
StatePublished - Oct 2021

Bibliographical note

Funding Information:
The authors thank the Center for Magnetic Resonance and Research's (CMRR UMN) Dr. D. Idiyatullin for MR-T1 scans on samples, S. Ramesh for processing tissue slices for analysis, C. Forster and A. Lewis from the Clinical and Translational Science Institute (CTSI UMN) for technical assistance with histology and imaging; M. Lotti for assistance with writing; Dr. N. Manuchehrabadi for help with supplementary rabbit nanowarming data. J.S.R. was supported by Schulze Diabetes Institute and Division of Transplantation at the Department of Surgery, University of Minnesota. The authors acknowledge Schulze Diabetes Institute, Department of Surgery for their confocal microscope. The authors would like to thank Dr. D. Bilardello at the Institute of Rock Magnetism (IRM) for his guidance in magnetic measurements. Part of this work was performed at the Institute for Rock Magnetism (IRM) at the University of Minnesota. The IRM is a US National Multi-user Facility supported through the Instrumentation and Facilities program of the National Science Foundation, Earth Sciences Division, and by funding from the University of Minnesota. The authors thank Y. Liu for her assistance with DLS measurements of sIONPs. The authors also thank the University Imaging Center (UIC) and Research Analytical laboratory (RAL) at UMN for technical assistance in imaging and ICP-OES measurements. This work was supported by the National Institutes of Health Grant 5R01DK117425-03 (J.C.B., E.B.F.), National Institute of Health Grant 5R01HL135046-04 (J.C.B., E.B.F.), and National Science Foundation Grant EEC 1941543 (J.C.B., E.B.F.). The views, opinions, and findings contained in this report are those of the authors and should not be construed as an official NIH or NSF position, policy, or decision unless so designated by other documentation.

Funding Information:
The authors thank the Center for Magnetic Resonance and Research's (CMRR UMN) Dr. D. Idiyatullin for MR‐T1 scans on samples, S. Ramesh for processing tissue slices for analysis, C. Forster and A. Lewis from the Clinical and Translational Science Institute (CTSI UMN) for technical assistance with histology and imaging; M. Lotti for assistance with writing; Dr. N. Manuchehrabadi for help with supplementary rabbit nanowarming data. J.S.R. was supported by Schulze Diabetes Institute and Division of Transplantation at the Department of Surgery, University of Minnesota. The authors acknowledge Schulze Diabetes Institute, Department of Surgery for their confocal microscope. The authors would like to thank Dr. D. Bilardello at the Institute of Rock Magnetism (IRM) for his guidance in magnetic measurements. Part of this work was performed at the Institute for Rock Magnetism (IRM) at the University of Minnesota. The IRM is a US National Multi‐user Facility supported through the Instrumentation and Facilities program of the National Science Foundation, Earth Sciences Division, and by funding from the University of Minnesota. The authors thank Y. Liu for her assistance with DLS measurements of sIONPs. The authors also thank the University Imaging Center (UIC) and Research Analytical laboratory (RAL) at UMN for technical assistance in imaging and ICP‐OES measurements. This work was supported by the National Institutes of Health Grant 5R01DK117425‐03 (J.C.B., E.B.F.), National Institute of Health Grant 5R01HL135046‐04 (J.C.B., E.B.F.), and National Science Foundation Grant EEC 1941543 (J.C.B., E.B.F.). The views, opinions, and findings contained in this report are those of the authors and should not be construed as an official NIH or NSF position, policy, or decision unless so designated by other documentation.

Publisher Copyright:
© 2021 The Authors. Advanced Science published by Wiley-VCH GmbH

Keywords

  • cryopreservation
  • iron oxide nanoparticles
  • kidney
  • perfusion
  • radiofrequency warming
  • vitrification

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