Irreversible Electroporation Using the Vasculature of an Organ as Fluid Electrodes

2012 ◽  
Author(s):  
Michael B. Sano ◽  
Christopher B. Arena ◽  
Paulo A. Garcia ◽  
Rafael V. Davalos
Keyword(s):  
Extracellular Matrix ◽  
Cell Death ◽  
Electric Fields ◽  
Bile Ducts ◽  
Electric Field Intensity ◽  
Irreversible Electroporation ◽  
Intensity Threshold ◽  
Nerve Conduits ◽  
Biophysical Process ◽  
And Function

Electroporation is a non-linear biophysical process in which the application of pulsed electric fields leads to an increase in permeability of cells, presumably through the creation of nanoscale pores in the lipid bilayer [1]. At low pulsing energy, this permeability is reversible and cellular health and function is maintained. Once a critical electric field intensity threshold is surpassed the cell membrane is unable to recover and cell death is induced in a precise and controllable manner with sub-millimeter resolution [2]. This process is referred to as irreversible electroporation (IRE). IRE does not rely on thermal mechanisms and preserves the structure of the underlying extracellular matrix (ECM) as well as nerve conduits and bile ducts [3].

scholarly journals The Effect of Conductivity Changes on Temperature Rise During Irreversible Electroporation

2020 ◽  
Author(s):  
Amir Khorasani
Keyword(s):  
Electrical Conductivity ◽  
Cell Death ◽  
Electric Field ◽  
Electric Field Intensity ◽  
Thermal Damage ◽  
Pulse Sequence ◽  
Irreversible Electroporation ◽  
Tissue Temperature ◽  
Comsol Multiphysics ◽  
Simulation Results

Purpose: Irreversible electroporation is a physical process which is used for killing the cancer cells. The process that leads to cell death in this method is a unique process. Thermal damage does not exist in this process. However, the temperature of the tissue also increases during the electroporation. In this study, we aim to investigate the effect of conductivity changes on tissue temperature increase during the irreversible electroporation process. Materials and Methods: To perform simulations and solve equations, COMSOL MultiPhysics has been used. Standard electroporation pulse sequence (8 pulses with different electric field intensities) was used as a pulse sequence in the simulation. Results: During the electroporation process, the electrical conductivity and the temperature of the tissue were increased. Changes in the tissue temperature in the simulation with variable electrical conductivity are more than in the simulation with constant electrical conductivity during the electroporation process. This difference for pulses with more vigorous electric field intensity and points closer to the electrodes has been achieved more. Conclusion: To more accurately estimate and calculate the temperature and thermal damage inside the tissue during the irreversible electroporation process, it is suggested to consider the effect of conductivity changes during this process.

Phase Change Electrodes for Reducing Joule Heating During Irreversible Electroporation

2012 ◽  
Author(s):  
Christopher B. Arena ◽  
Roop L. Mahajan ◽  
Marissa Nichole Rylander ◽  
Rafael V. Davalos
Keyword(s):  
Cell Death ◽  
Electric Fields ◽  
Electric Field Distribution ◽  
Irreversible Electroporation ◽  
Tissue Ablation ◽  
Thermal Processes ◽  
Ablation Volume ◽  
Extracellular Matrix Components ◽  
Membrane Defects ◽  
Viable Treatment

Irreversible electroporation (IRE) is a non-thermal tissue ablation modality that is gaining momentum as a viable treatment option for tumors and other non-cancerous pathologies [1]. The protocol consists of delivering a series of short (∼ 100 μs) and intense (∼ 1000 V/cm) pulsed electric fields through electrodes inserted directly into or around a targeted tissue. The pulses induce a rapid buildup of charge across the plasma membrane of cells comprising the tissue that results in the creation of permanent membrane defects, ultimately leading to cell death. Because the extent of cell death relies predominately on the extent of charge buildup and not thermal processes, extracellular matrix components are spared, including major nerve and blood vessel architecture. Additionally, the ablation volume is predictable based on the electric field distribution and visible in real-time via MRI, CT, and ultrasound.

scholarly journals Towards Solid Tumor Treatment by Nanosecond Pulsed Electric Fields

2009 ◽  
Vol 8 (4) ◽  
pp. 289-306 ◽  
Author(s):  
Axel T. Esser ◽  
Kyle C. Smith ◽  
T. R. Gowrishankar ◽  
James C. Weaver
Keyword(s):  
Cell Death ◽  
Electric Field ◽  
Spatial Scale ◽  
Electric Fields ◽  
Solid Tumor ◽  
Irreversible Electroporation ◽  
Pulsed Electric Fields ◽  
Underlying Mechanism ◽  
Tumor Ablation ◽  
Nanosecond Pulsed Electric Fields

Local and drug-free solid tumor ablation by large nanosecond pulsed electric fields leads to supra-electroporation of all cellular membranes and has been observed to trigger nonthermal cell death by apoptosis. To establish pore-based effects as the underlying mechanism inducing apoptosis, we use a multicellular system model (spatial scale 100 μm) that has irregularly shaped liver cells and a multiscale liver tissue model (spatial scale 200 mm). Pore histograms for the multicellular model demonstrate the presence of only nanometer-sized pores due to nanosecond electric field pulses. The number of pores in the plasma membrane is such that the average tissue conductance during nanosecond electric field pulses is even higher than for longer irreversible electroporation pulses. It is shown, however, that these nanometer-sized pores, although numerous, only significantly change the permeability of the cellular membranes to small ions, but not to larger molecules. Tumor ablation by nanosecond pulsed electric fields causes small to moderate temperature increases. Thus, the underlying mechanism(s) that trigger cell death by apoptosis must be non-thermal electrical interactions, presumably leading to different ionic and molecular transport than for much longer irreversible electroporation pulses.

Enhanced Structure and Function of Stem Cell-Derived Beta-Like Cells Cultured on Extracellular Matrix

2020 ◽  
Author(s):  
Reena Singh ◽  
Richard Tan ◽  
Clara Tran ◽  
Thomas Loudovaris ◽  
Helen E. Thomas ◽  
...  
Keyword(s):  
Extracellular Matrix ◽  
Stem Cell ◽  
Structure And Function ◽  
And Function ◽  
Cells Cultured

Assessment of Chronological Effects of Irreversible Electroporation on Hilar Bile Ducts in a Porcine Model

2013 ◽  
Vol 37 (1) ◽  
pp. 224-230 ◽  
Author(s):  
Jae Woong Choi ◽  
David S. K. Lu ◽  
Ferdnand Osuagwu ◽  
Steven Raman ◽  
Charles Lassman
Keyword(s):  
Bile Ducts ◽  
Porcine Model ◽  
Irreversible Electroporation

scholarly journals Proteolytic Events of Wound-Healing — Coordinated Interactions Among Matrix Metalloproteinases (MMPs), Integrins, and Extracellular Matrix Molecules

2001 ◽  
Vol 12 (5) ◽  
pp. 373-398 ◽  
Author(s):  
Bjorn Steffensen ◽  
Lari Häkkinen ◽  
Hannu Larjava
Keyword(s):  
Extracellular Matrix ◽  
Wound Healing ◽  
Matrix Metalloproteinases ◽  
Wound Repair ◽  
Enzyme Activation ◽  
Processing Enzymes ◽  
The Matrix ◽  
Signaling Receptors ◽  
State Of Rest ◽  
And Function

During wound-healing, cells are required to migrate rapidly into the wound site via a proteolytically generated pathway in the provisional matrix, to produce new extracellular matrix, and, subsequently, to remodel the newly formed tissue matrix during the maturation phase. Two classes of molecules cooperate closely to achieve this goal, namely, the matrix adhesion and signaling receptors, the integrins, and matrix-degrading and -processing enzymes, the matrix metalloproteinases (MMPs). There is now substantial experimental evidence that blocking key molecules of either group will prevent or seriously delay wound-healing. It has been known for some time now that cell adhesion by means of the integrins regulates the expression of MMPs. In addition, certain MMPs can bind to integrins or other receptors on the cell surface involved in enzyme activation, thereby providing a mechanism for localized matrix degradation. By proteolytically modifying the existing matrix molecules, the MMPs can then induce changes in cell behavior and function from a state of rest to migration. During wound repair, the expression of integrins and MMPs is simultaneously up-regulated. This review will focus on those aspects of the extensive knowledge of fibroblast and keratinocyte MMPs and integrins in biological processes that relate to wound-healing.

Regulation of human lung fibroblast phenotype and function by vitronectin and vitronectin integrins

2001 ◽  
Vol 114 (19) ◽  
pp. 3507-3516 ◽  
Author(s):  
Amelia K. Scaffidi ◽  
Yuben P. Moodley ◽  
Markus Weichselbaum ◽  
Philip J. Thompson ◽  
Darryl A. Knight
Keyword(s):  
Extracellular Matrix ◽  
Smooth Muscle ◽  
Monoclonal Antibodies ◽  
Human Lung ◽  
Stress Fibers ◽  
Collagen Gels ◽  
Human Lung Fibroblast ◽  
Myofibroblast Phenotype ◽  
And Function ◽  
Blocking Antibodies

Myofibroblasts, characterised by high expression of α-smooth muscle actin (α-SMA), are important and transient cells in normal wound healing but are found in increased number in various pathological conditions of the lung including asthma and pulmonary fibrosis. The mechanisms that regulate the myofibroblast phenotype are unknown but are likely to involve signals from the extracellular matrix transmitted via specific integrins. Vitronectin is a glycoprotein released during inflammation and has been shown to regulate the phenotype of vascular smooth muscle cells via αv and β1 integrins. In the current study we have examined whether vitronectin influences the phenotype and function of normal human lung fibroblasts (HFL-1). Incubation of HFL-1 cells with vitronectin induced a concentration-dependent reduction in α-SMA expression. By contrast, function-blocking monoclonal antibodies to the vitronectin integrins αv, β1, αvβ3 and αvβ5 induced the expression of α-SMA and its organization into stress fibers. Expression of α-SMA induced by all function-blocking monoclonal antibodies was abrogated by inhibition of protein kinase C and phosphatidylinositol-3 kinase, but the effects of inhibition of other signalling pathways was integrin dependent. Exposure to other extracellular matrix proteins such as fibronectin, collagen or their integrins did not influence expression of α-SMA. The expression and organization of α-SMA induced by exposure to function-blocking antibodies was translated into an augmented capacity of HFL-1 cells to contract fibroblast populated collagen gels. By contrast, contraction of collagen gels following incubation with vitronectin was not significantly different to control. This study has shown that vitronectin influences the phenotype and behaviour of HFL-1 cells by downregulating the expression of α-SMA and reducing their contractile ability. By contrast, occupancy of specific integrins by function-blocking antibodies upregulated the expression of α-SMA and induced the formation of functional stress fibers capable of contracting collagen gels. These results suggest that vitronectin modulates the fibroblast-myofibroblast phenotype, implying an important role in the remodelling process during lung development or response to injury.

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