Multiple cryoprotectant toxicity model for vitrification solution optimization.
Cryopreservation
Cryoprotectants
Optimization
Sloppy models
Toxicity
Vitrification
Journal
Cryobiology
ISSN: 1090-2392
Titre abrégé: Cryobiology
Pays: Netherlands
ID NLM: 0006252
Informations de publication
Date de publication:
10 2022
10 2022
Historique:
received:
17
05
2022
revised:
05
08
2022
accepted:
07
09
2022
pubmed:
17
9
2022
medline:
5
10
2022
entrez:
16
9
2022
Statut:
ppublish
Résumé
Vitrification is a promising cryopreservation technique for complex specimens such as tissues and organs. However, it is challenging to identify mixtures of cryoprotectants (CPAs) that prevent ice formation without exerting excessive toxicity. In this work, we developed a multi-CPA toxicity model that predicts the toxicity kinetics of mixtures containing five of the most common CPAs used in the field (glycerol, dimethyl sulfoxide (DMSO), propylene glycol, ethylene glycol, and formamide). The model accounts for specific toxicity, non-specific toxicity, and interactions between CPAs. The proposed model shows reasonable agreement with training data for single and binary CPA solutions, as well as ternary CPA solution validation data. Sloppy model analysis was used to examine the model parameters that were most important for predictions, providing clues about mechanisms of toxicity. This analysis revealed that the model terms for non-specific toxicity were particularly important, especially the non-specific toxicity of propylene glycol, as well as model terms for specific toxicity of formamide and interactions between formamide and glycerol. To demonstrate the potential for model-based design of vitrification methods, we paired the multi-CPA toxicity model with a published vitrification/devitrification model to identify vitrifiable CPA mixtures that are predicted to have minimal toxicity. The resulting optimized vitrification solution composition was a mixture of 7.4 molal glycerol, 1.4 molal DMSO, and 2.4 molal formamide. This demonstrates the potential for mathematical optimization of vitrification solution composition and sets the stage for future studies to optimize the complete vitrification process, including CPA mixture composition and CPA addition and removal methods.
Identifiants
pubmed: 36113568
pii: S0011-2240(22)00094-3
doi: 10.1016/j.cryobiol.2022.09.002
pmc: PMC9529850
mid: NIHMS1837459
pii:
doi:
Substances chimiques
Cryoprotective Agents
0
Formamides
0
Ice
0
formamide
4781T907ZS
Propylene Glycol
6DC9Q167V3
Ethylene Glycol
FC72KVT52F
Glycerol
PDC6A3C0OX
Dimethyl Sulfoxide
YOW8V9698H
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Research Support, N.I.H., Extramural
Langues
eng
Sous-ensembles de citation
IM
Pagination
1-9Subventions
Organisme : NIBIB NIH HHS
ID : R01 EB027203
Pays : United States
Informations de copyright
Copyright © 2022 Elsevier Inc. All rights reserved.
Déclaration de conflit d'intérêts
Declaration of competing interest The authors have no conflicts of interest.
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