Evidence map›Paper›PMID 33157080›Full record

ArticleCryobiology2021

Rapid quantification of multi-cryoprotectant toxicity using an automated liquid handling method.

Ross M Warner, Emi Ampo, Dylan Nelson, James D Benson, Ali Eroglu, Adam Z Higgins

Open access · greenAbstract read
In one paragraph

Article in Cryobiology, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 21 papers.

0numbers the graph read from it
0cells of the map it votes in
21citing papers in PubMed
3.4field-weighted citation impact, top 7% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

21 citing papers in PubMed, 42 citations in OpenAlex.

  1. Article
  2. Lessons From Drug Discovery for Cryoprotective Agent Design: An AI-Oriented Perspective.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026
    Article
  3. Article
  4. Article
  5. Article
  6. Article
  7. A size-dependent ideal solution model for liquid-solid phase equilibria prediction in aqueous organic solutions.Proceedings of the National Academy of Sciences of the United States of America · 2025
    Article
  8. Article
  9. Article
  10. Article
  11. Article
  12. Zebrafish as a high throughput model for organ preservation and transplantation research.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2023
    Article
  13. Article
  14. Article
  15. Technologies for Vitrification Based Cryopreservation.Bioengineering (Basel, Switzerland) · 2023
    Review
  16. Review
  17. Article
  18. Chemical approaches to cryopreservation.Nature reviews. Chemistry · 2022
    Review
  19. Review
  20. Article
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

6 authors at 3 institutions in 2 countries.

Ross M WarnerSchool of Chemical, Biological and Environmental Engineering, Oregon State University, Corvallis, OR, USA.
Emi AmpoSchool of Chemical, Biological and Environmental Engineering, Oregon State University, Corvallis, OR, USA.
Dylan NelsonCollege of Pharmacy, Oregon State University, Corvallis, OR, USA.
James D BensonDepartment of Biology, University of Saskatchewan, Saskatoon, SK, Canada.
Ali ErogluDepartment of Neuroscience and Regenerative Medicine, Medical College of Georgia, Augusta University, Augusta, GA, USA.
Adam Z HigginsSchool of Chemical, Biological and Environmental Engineering, Oregon State University, Corvallis, OR, USA. Electronic address: adam.higgins@oregonstate.edu.
Oregon State University · USAugusta University · USUniversity of Saskatchewan · CA

Funding

Viable Banking of Human TissuesR01EB027203 · NIBIB · AUGUSTA UNIVERSITY · PI EROGLU, ALI · 2018 to 2021
$1.5M
NIBIB NIH HHS R01 EB027203
6 · The paper itself

Abstract

Cryopreservation in a vitrified state has vast potential for long-term storage of tissues and organs that may be damaged by ice formation. However, the toxicity imparted by the high concentration of cryoprotectants (CPAs) required to vitrify these specimens remains a hurdle. To address this challenge, we previously developed a mathematical approach to design less toxic CPA equilibration methods based on the minimization of a toxicity cost function. This approach was used to design improved methods for equilibration of bovine pulmonary artery endothelial cells (BPAEC) with glycerol. To fully capitalize on the toxicity cost function approach, it is critical to describe the toxicity kinetics of additional CPAs, including multi-CPA mixtures that are commonly used for vitrification. In this work, we used automated liquid handling to characterize the toxicity kinetics of five of the most common CPAs (glycerol, dimethyl sulfoxide (DMSO), propylene glycol, ethylene glycol, and formamide), along with their binary and ternary mixtures for BPAEC. In doing so, we developed experimental methods that can be used to determine toxicity kinetics more quickly and accurately. Our results highlight some common CPA toxicity trends, including the relatively low toxicity of ethylene glycol and a general increase in toxicity as the CPA concentration increases. Our results also suggest potential new approaches to reduce toxicity, including a surprising toxicity neutralization effect of glycerol on formamide. In the future, this dataset will serve as the basis to expand our CPA toxicity model, enabling application of the toxicity cost function approach to vitrification solutions containing multiple CPAs.

Indexed as

CryopreservationEndothelial CellsAnimalsCattleCryoprotective AgentsDimethyl SulfoxideEthylene GlycolVitrificationCryoprotective AgentsDimethyl SulfoxideEthylene GlycolAutomated liquid handlingCell viabilityCryoprotectantsToxicityVitrification

Identifiers

PMID33157080
PMCPMC7897298
OpenAlexW3095430694

What OpenQuestion holds

Textmetadata
LicenceTDM
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.