Implications of variability in cell membrane permeability for design of methods to remove glycerol from frozen-thawed erythrocytes

Lahmann, John M.; Sanchez, Cynthia Cruz; Benson, James D.; Acker, Jason P.; Higgins, Adam Z.

doi:10.1016/j.cryobiol.2020.01.006

Cited by 7 publications

(3 citation statements)

References 66 publications

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“…Analytical mass transport models have been widely used to simulate cell volume responses and CPA uptake during the exposure of cells to CPA solutions 5,6,8,19 . Modeling predictions can be used to avoid conditions that cause cells to shrink or swell beyond their osmotic tolerance limits and to compute the time needed to reach a sufficiently high enough intracellular CPA concentration to protect against freezing injury 11 .…”

Section: Discussionmentioning

confidence: 99%

Loading equine oocytes with cryoprotective agents captured with a finite element method model

Içli

Soleimani

Oldenhof

et al. 2021

Sci Rep

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Cryopreservation can be used to store equine oocytes for extended periods so that they can be used in artificial reproduction technologies at a desired time point. It requires use of cryoprotective agents (CPAs) to protect the oocytes against freezing injury. The intracellular introduction of CPAs, however, may cause irreversible osmotic damage. The response of cells exposed to CPA solutions is governed by the permeability of the cellular membrane towards water and the CPAs. In this study, a mathematical mass transport model describing the permeation of water and CPAs across an oocyte membrane was used to simulate oocyte volume responses and concomitant intracellular CPA concentrations during the exposure of oocytes to CPA solutions. The results of the analytical simulations were subsequently used to develop a phenomenological finite element method (FEM) continuum model to capture the response of oocytes exposed to CPA solutions with spatial information. FEM simulations were used to depict spatial differences in CPA concentration during CPA permeation, namely at locations near the membrane surface and towards the middle of the cell, and to capture corresponding changes in deformation and hydrostatic pressure. FEM simulations of the multiple processes occurring during CPA loading of oocytes are a valuable tool to increase our understanding of the mechanisms underlying cryopreservation outcome.

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Section: Discussionmentioning

confidence: 99%

Loading equine oocytes with cryoprotective agents captured with a finite element method model

Içli

Soleimani

Oldenhof

et al. 2021

Sci Rep

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show abstract

“…Current evidence suggested the presence of RBC sub-populations (e.g., oldest cells [31]) less resilient to cryopreservation-related injuries. The high variability in the glycerol permeability of the RBC membrane, and thus in the hemolysis after deglycerolization, between donors and within cells from the same donor [55], is further indicative of samples with low responsiveness to cryopreservation. In similarity to the currently known donor effects on the refrigerated storage lesion [56], small-scale studies at first, and then large donor-recipient cohorts studies are needed to understand the impact of donor factors on the efficacy and safety of frozen RBCs.…”

Section: What Nextmentioning

confidence: 99%

When I need you most: frozen red blood cells for transfusion

Anastasiadi

Tzounakas

Kriebardis

et al. 2020

Transfusion and Apheresis Science

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“…The need for greatly improved cryopreservation strategies for cells and tissues has increased dramatically during the past decade and this need has been driven by numerous advances in cellular and regenerative therapies [1][2][3][4]. Current cryopreservation strategies often employ a cryoprotective agent (CPA) such as dimethyl sulfoxide (DMSO) and glycerol [5][6][7][8][9][10][11][12][13][14]. These CPAs offer varying degrees of protection against the cellular injury associated with cryopreservation [15,16].…”

Section: Introductionmentioning

confidence: 99%

Investigating the Solubility and Activity of a Novel Class of Ice Recrystallization Inhibitors

2021

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O-aryl-β-D-glucosides and N-alkyl-D-gluconamides are two classes of effective ice recrystallization inhibitors (IRIs), however their solubilities limit their use in cryopreservation applications. Herein, we have synthesized and assessed phosphonate analogues of small-molecule IRIs as a method to improve their chemical and physical properties. Four sodium phosphonate compounds 4–7 were synthesized and exhibited high solubilities greater than 200 mM. Their IRI activity was evaluated using the splat cooling assay and only the sodium phosphonate derivatives of α-methyl-D-glucoside (5-Na) and N-octyl-D-gluconamide (7-Na) exhibited an IC50 value less than 30 mM. It was found that the addition of a polar sodium phosphonate group to the alkyl gluconamide (1) and aryl glucoside (2) structure decreased its IRI activity, indicating the importance of a delicate hydrophobic/hydrophilic balance within these compounds. The evaluation of various cation-phosphonate pairs was studied and revealed the IRI activity of ammonium and its ability to modulate the IRI activity of its paired anion. A preliminary cytotoxicity study was also performed in a HepG2 cell line and phosphonate analogues were found to have relatively low cytotoxicity. As such, we present phosphonate small-molecule carbohydrates as a biocompatible novel class of IRIs with high solubilities and moderate-to-high IRI activities.

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Implications of variability in cell membrane permeability for design of methods to remove glycerol from frozen-thawed erythrocytes

Cited by 7 publications

References 66 publications

Loading equine oocytes with cryoprotective agents captured with a finite element method model

Loading equine oocytes with cryoprotective agents captured with a finite element method model

When I need you most: frozen red blood cells for transfusion

Investigating the Solubility and Activity of a Novel Class of Ice Recrystallization Inhibitors

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