Cryoprotectant Toxicity: Facts, Issues, and Questions

Best, Benjamin P.

doi:10.1089/rej.2014.1656

Cited by 391 publications

(317 citation statements)

References 175 publications

(226 reference statements)

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“…Major cell damages caused by CPA toxicity are lists as follows: (i) cell membranes are breached or damaged; (ii) enzyme function is impaired; (iii) cell development or proliferation is diminished; (iv) mitochondrial function is reduced; (v) DNA, proteins, or other macromolecules are damaged44. These damages will directly induce the dysfunction of cell behaviors, such as attachment or proliferation.…”

Section: Resultsmentioning

confidence: 99%

Natural zwitterionic betaine enables cells to survive ultrarapid cryopreservation

Yang

Cai

Zhai

et al. 2016

Sci Rep

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Cryoprotectants (CPAs) play a critical role in cryopreservation because they can resist the cell damage caused by the freezing process. Current state-of-the-art CPAs are mainly based on an organic solvent dimethyl sulfoxide (DMSO), and several DMSO-cryopreserved cell products have been brought to market. However, the intrinsic toxicity and complex freezing protocol of DMSO still remain as the bottleneck of the wide use for clinical applications. Herein, we reported that betaine, a natural zwitterionic molecule, could serve as a nontoxic and high efficient CPA. At optimum concentration of betaine, different cell types exhibited exceptional post-thaw survival efficiency with ultrarapid freezing protocol, which was straightforward, cost efficient but difficult to succeed using DMSO. Moreover, betaine showed negligible cytotoxicity even after long-term exposure of cells. Mechanistically, we hypothesized that betaine could be ultra-rapidly taken up by cells for intracellular protection during the freezing process. This technology unlocks the possibility of alternating the traditional toxic CPAs and is applicable to a variety of clinical applications.

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Section: Resultsmentioning

confidence: 99%

Natural zwitterionic betaine enables cells to survive ultrarapid cryopreservation

Yang

Cai

Zhai

et al. 2016

Sci Rep

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“…It is possible that if we use another cryopreservation media formulation like hydroxyethyl starch (HES) mixed with fetal bovine serum (FBS) or dimethyl sulfoxide (DMSO) and sucrose, the different of parasitaemia percentage in all storage times will be insignificant. DMSO and glycerol are the most common used as cryoprotective agents (CPAs) to eliminate ice formation when cooling cells or organs to cryogenic temperatures [14][15][16]. In DMSO and glycerol the mechanism of protective effect on frozen cells occurs by intracellular permeation.…”

Section: Resultsmentioning

confidence: 99%

<em>In Vitro</em> Infectivity Study of Cryopreserved Irradiated Intraerythrocytic Form of <em>Plasmodium falciparum</em>

et al. 2017

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In control human malaria infection studies using irradiated Plasmodium falciparum, the cell bank of irradiated P. falciparum infected erythrocytes is needed. The cell banking methods represent an obvious way to obtain suitable material for blood stage Plasmodium. In a cell bank development of irradiated Plasmodium infected erythrocytes, the ability to cryopreserve procedure of Plasmodium is important to recover the infectivity of irradiated Plasmodium. This study aims at evaluating the in vitro infectivity of cryopreserved irradiated intra-erythrocytic form of P. falciparum. A protein profile investigation using Sodium Dodecyl SulfatePolyacrylamide Gel Electrophoresis (SDS-PAGE) of cryopreserved irradiated P. falciparum also conducted in this study to know the cryopreserved effect on the protein of irradiated P. falciparum. Plasmodium falciparum of 3D7 strain in human erythrocytes was maintained in in vitro continuous culture. When the percentage of parasites was 1020 %, the culture was harvested and irradiated with gamma rays at a dose of 175 Gy. Irradiated P. falciparum then was mixed with cryopreserved solution and stored in -80 °C for one hour before transferred into liquid nitrogen for 20, 40 and 60 days. After being stored the irradiated P. falciparum was thawed and cultured for 20 days. The percentage of parasitaemia was enumerated by examining Giemsa stained thin blood films prepared for 20 days after initiation of culture. Results showed that storage time significantly (p<0.05) influence the percentage of parasitaemia. The cooling procedure and cryopreservation media may affect this study results. It also showed that there was insignificant difference of irradiated P. falciparum protein profile in all storage times. Overall it can be assumed that the irradiated P. falciparum still kept their infectivity after stored in liquid nitrogen for 60 days. Further study using different cooling procedure and different formula of cryopreservation media with a longer storage time should be conduct to validate this study results. There were different targets in malaria cycle for developing malaria vaccines. Pre-erythrocytic Atom Indonesia Vol. 43 No. 3 (2017) 167 -171 Atom Indonesia Journal homepage: http://aij.batan.go.id 167 S. Nurhayati et al. / Atom Indonesia Vol. 43 No. 3 (2017) 167 -171 11 vaccine aims to prevent sporozoites entry and develop in the liver, while asexual blood-stage vaccine prevents disease by targeting merozoite invasion and intra-erythrocytic development; and the transmission-blocking vaccine targets on the sexual and sporogonic stages to prevent parasite development in the mosquito [2].Eventhough developing a vaccine using ionizing radiation has some advantage because it can remove chemical contaminants and penetrate pathogens to damage the DNA, but it has not been pursued avidly over the past 20 years. There are two reasons why radiation technology was no longer used in vaccine development. First, the development of new radiation techniques has been considered impractical or di...

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“…Chemical toxicity is another potentially damaging factor that must be considered; both in the choice of CPA and in the concentration used [40]. While few toxic events have been linked to non-penetrating CPA, the ability of the penetrating CPAs to enter the cell, where they can interact with cellular processes, makes this class of compound more likely to demonstrate cellular toxicity.…”

Section: Choice Of Cpamentioning

confidence: 99%

Technical Considerations in the Freezing, Low-Temperature Storage and Thawing of Stem Cells for Cellular Therapies

Hunt¹

2019

Transfus Med Hemother

105

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The commercial and clinical development of cellular therapy products will invariably require cryopreservation and frozen storage of cellular starting materials, intermediates and/or final product. Optimising cryopreservation is as important as optimisation of the cell culture process in obtaining maximum yield and a consistent end-product. Suboptimal cryopreservation can lead not only to batch-to-batch variation, lowered cellular functionality and reduced cell yield, but also to the potential selection of subpopulations with genetic or epigenetic characteristics divergent from the original cell line. Regulatory requirements also impact on cryopreservation as these will require a robust and reproducible approach to the freezing, storage and thawing of the product. This requires attention to all aspects of the application of low temperatures: from the choice of freezing container and cryoprotectant, the cooling rate employed and its mode of delivery, the correct handling of the frozen material during storage and transportation, to the eventual thawing of the product by the end-user. Each of these influences all of the others to a greater or lesser extent and none should be ignored. This paper seeks to provide practical insights and alternative solutions to the technical challenges faced during cryopreservation of cells for use in cellular therapies.

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Cryoprotectant Toxicity: Facts, Issues, and Questions

Cited by 391 publications

References 175 publications

Natural zwitterionic betaine enables cells to survive ultrarapid cryopreservation

Natural zwitterionic betaine enables cells to survive ultrarapid cryopreservation

<em>In Vitro</em> Infectivity Study of Cryopreserved Irradiated Intraerythrocytic Form of <em>Plasmodium falciparum</em>

Technical Considerations in the Freezing, Low-Temperature Storage and Thawing of Stem Cells for Cellular Therapies

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