Transport phenomena during freezing of isolated hepatocytes

Toner, Mehmet; Tompkins, Ronald G.; Cravalho, E.G.; Yarmush, Martin L.

doi:10.1002/aic.690381004

Cited by 62 publications

(63 citation statements)

References 36 publications

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“…On the other hand, Refs. [14][15][16][17][18][19] take into account only the simulation of IIF with the goal of evaluating the ice nucleation and growth parameters. Here, only water osmosis during freezing is taken into account by means of the Mazur's equation.…”

Section: Introductionmentioning

confidence: 99%

“…In this case, the modeling of the equilibration phase is circumvented by simply replacing some of the intracellular water with the exact amount of CPA necessary to obtain an equal value of its internal and external concentrations, while IIF is either accounted for as taking place within a single representative (i.e., average) cell 17 or the probability of IIF (PIIF) is related to the nucleation rate by assuming sporadic nucleation of identical cells. 15 Recently, a novel model based on population balance equations (PBEs) approach is proposed to quantitatively interpret the behavior of a population of biological cells during the cooling stage of a cryopreservation procedure in the absence of CPA. 20 Specifically, the natural size distribution of a population of cells of the same lineage was invoked to interpret the experimental evidence that IIF takes place at different temperatures, depending on the specific operative conditions adopted.…”

Section: Introductionmentioning

confidence: 99%

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Rationalizing the equilibration and cooling stages of cryopreservation: The effect of cell size distribution

2011

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A novel model able to quantitatively describe intracellular ice formation (IIF) as a function of temperature in a cell population characterized by a size distribution is proposed for the case when a permeant cryoprotectant agent (CPA) is present. As such, the model represents the ideal extension of the one recently proposed by the authors for interpreting the behavior of a size-distributed population of cells during cryopreservation without CPA. To resemble the experimental procedure actually adopted, the former model is coherently modified for the simulation of the initial equilibration stage (i.e., a one-step CPA permeation kinetics into cells initially under isotonic conditions to be suspended in a water/salt/CPA solution at ambient temperature) and of the subsequent cooling stage at constant rate down to À60 C. Specifically, the size distribution dynamics of a cell population in response to water osmosis, CPA permeation, and IIF is simulated by means of a suitable population balance approach. Water and CPA intracellular transport equations based on the classical Kedem and Katchalsky formalism are coupled to the quantitative description of nucleation and diffusion-limited growth of ice crystals in the framework of a one-dimensional population balance equation. The driving forces of all the physico-chemical phenomena involved are evaluated by taking into account the relevant ternary phase diagram, whereas the viscosity of the cytoplasm solution is properly accounted as a function of the salt and CPA concentrations. After a reasoned choice of the values of model parameters, the behavior of isolated rat hepatocytes suspended in a water/sodium-chloride/glycerol solution is simulated and analyzed at different, practicable (i.e., low) constant cooling rates and CPA equilibration concentrations. It is confirmed that differently sized cells in a single population exhibit different IIF temperatures under the same operative conditions even Correspondence concerning this article should be addressed to A. Cincotti at cincotti@dicm.unica.it or G. Cao at cao@visnu.dicm.unica.it. BIOENGINEERING, FOOD, AND NATURAL PRODUCTSin the presence of CPA. Correspondingly, the probability of IIF results to be a function of the initial size distribution of the cell population. Depending on the specific operative conditions adopted, the size distribution and the osmotic properties of the cell lineage at hand, IIF at À60 C may be lethal for a fraction of the cell population (i.e., larger size classes), or it may not reach a dangerous level for the intermediate size class cells, while it will not even take place for the smaller ones. Finally, even if no comparison with experimental data is provided, an original and physically sound explanation for several, well-known experimental evidences, which appeared in a number of articles available in the literature of cell cryopreservation with CPA, is comprehensively given.

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Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Rationalizing the equilibration and cooling stages of cryopreservation: The effect of cell size distribution

2011

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“…As with most mammalian cells, it is assumed that the hydrostatic or turgor pressure across the cell mem brane is negligible. A more complete discussion of the assumptions behind this model and the errors associated with these assumptions can be found in Toner et al (38).…”

Section: Water Transport Modelmentioning

confidence: 99%

“…Furthermore, the permeability of the membrane is rate limited by the passage of water through the cell membrane. Assuming an Arrhenius re lationship (19,20,38), the permeability is expressed as a function of temperature…”

Section: Water Transport Modelmentioning

confidence: 99%

Freezing Characteristics of Genetically Modified Lymphocytes for the Treatment of MPS II

1999

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The freezing characteristics of genetically modified lymphocytes obtained from a donor with mucopolysac charidosis type II (MPS II) were determined using cryomicroscopy and controlled rate freezing studies to determine postthaw viability. The cells from a donor with MPS II used in this investigation were cultured and transduced with a retroviral vector for the iduronate-2-sulfatase (IDS) enzyme for clinical studies for human gene therapy. The water transport and intracellular ice formation (IIF) characteristics of the cells were determined after completion of the culture and transduction protocol. The water transport parameters, L m and £, p , for the cultured and transduced cells were determined to be 4.4 ± 1.3 x 10~1 4 m 3 /Ns and 173 ± 25 kJ/mol, respectively. The IIF nucleation parameters, K and Q, were 5.5 x 10 10 K 5 and 3.5 x 10" (1/m 2 s), respectively. The postthaw viability of the genetically modified cells was less than the viability of the freshly isolated cells from the same donor. The postthaw viability of the cultured and transduced cells from a donor with MPS II was also less than that observed with cells from a normal donor that were frozen and thawed under the same conditions. These studies are essential in understanding the biophysical changes resulting from the ex vivo culture of cells and the manner in which these changes influence the ability of the cells to be cryopreserved.

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“…Nucleation of intracellular ice can be catalyzed by either a surface (surface catalyzed nucleation, SCN) such as the cell plasma membrane or a volume of subcooled solution (volume catalyzed nucleation, VCN) such as the cytoplasm (Hobbs 1974;Toner 1993). The rate of ice nucleation (I) due to either VCN or SCN can be estimated as follows (Toner et al 1990;Toner et al 1992):…”

Section: Biophysics In Cell Preservationmentioning

confidence: 99%

Preservation of Embryonic Stem Cells

He¹

2011

Methodological Advances in the Culture, Manipulation and Utilization of Embryonic Stem Cells for Basic and Practical Applicatio

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Transport phenomena during freezing of isolated hepatocytes

Cited by 62 publications

References 36 publications

Rationalizing the equilibration and cooling stages of cryopreservation: The effect of cell size distribution

Rationalizing the equilibration and cooling stages of cryopreservation: The effect of cell size distribution

Freezing Characteristics of Genetically Modified Lymphocytes for the Treatment of MPS II

Preservation of Embryonic Stem Cells

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