Using Non-Thermal Irreversible Electroporation to create an in Vivo Niche for Exogenous Cell Engraftment

Chang, Tzu-Ming; Zhou, Vivian X.; Rubinsky, Boris

doi:10.2144/000114547

Cited by 25 publications

(21 citation statements)

References 14 publications

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“…Recently [1], we have pioneered “minimally invasive regenerative surgery” (MIRS) as a new medical modality that could become an alternative to whole organ transplant for treatment of end-stage organ failures, such as the liver, or for treatment of impaired organ function, such as diabetes. MIRS employs non-thermal irreversible electroporation (NTIRE), to create an in vivo niche of a decellularized intact extracellular matrix for exogenous cell engraftment [1]. Electroporation, is the permeabilization of the cell membrane with electric fields, delivered across a cell [2].…”

Section: Introductionmentioning

confidence: 99%

Molecular and histological study on the effects of non-thermal irreversible electroporation on the liver

Zhang

Lyu

Liu

et al. 2018

Biochemical and Biophysical Research Communications

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Non-thermal irreversible electroporation (NTIRE) is a biophysical phenomenon in which certain electric fields delivered across the cell membrane in tissue, cause cell death, without affecting the extracellular matrix. "Minimally invasive regenerative surgery" is a new medical modality for treatment of end-stage organ or tissue failure in which exogenous cells are implanted in a decellularized niche in tissue, formed by the delivery of NTIRE electric fields across a targeted volume of tissue. We anticipate that the success of the procedure will depend on the time of implantation relative to the application of NTIRE. This study was performed to elucidate the histological and molecular events that occur within 24 h after NTIRE, in the context of optimal criteria for the time of implantation. To this end, we examined the histology of NTIRE treated rat liver with H&E, Masson trichrome and TUNEL staining. Western blot was used to examine pro and cleaved caspase-3 (marker for apoptosis), pro and cleaved caspase-1 and gasdermin D (markers for pyroptosis), and RIP3 and MLKL (markers for necroptosis). The key findings are that, complete hepatocytes disintegration within an intact extracellular matrix is seen at 6 h and, new hepatocytes are seen in the treated region at 24 h, after NTIRE. There is no evidence of apoptotic cell death from NTIRE, contrary to commonly made claims in the NTIRE literature. However, molecular pathways of pyroptosis and necroptosis, programed necrosis associated with inflammation, are activated at 6 h after NTIRE and are not evident at 24 h after NTIRE. These are fundamental new findings of basic value to the field of NTIRE in all its applications. Taken together the results suggest the hypothesis that an optimal time for implantation is about 24 h after NTIRE. Future studies in which exogenous cells are implanted at different times after NTIRE are required to examine this hypothesis.

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Section: Introductionmentioning

confidence: 99%

Molecular and histological study on the effects of non-thermal irreversible electroporation on the liver

Zhang

Lyu

Liu

et al. 2018

Biochemical and Biophysical Research Communications

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“…9 panel B1, but not as severe compared to 24h post treatment, though direct comparison is difficult due to different grades of dilatation of the sinusoids of both controls and treated lesions. Note how vessels remain intact in these experiments as well (arrows), while there appears to be an increase in fibrous tissue in the top left corner of the micrograph (left side of dashed lines, see high resolution images in supplementary data), indicating regeneration processes of the liver, which is a known phenomenon also from other electroporation based ablation technologies 48,49 .…”

Section: Temporal Histology After Treatment With An E2 Waveformmentioning

confidence: 65%

Peer Review #2 of "Toward a clinical real time tissue ablation technology: combining electroporation and electrolysis (E2) (v0.2)"

2020

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Background: Percutaneous image-guided tissue ablation (IGA) plays a growing role in the clinical management of solid malignancies. Electroporation is used for IGA in several modalities: irreversible electroporation (IRE), and reversible electroporation with chemotoxic drugs, called electrochemotherapy (ECT). It was shown that the combination of electrolysis and electroporation-E2-affords tissue ablation with greater efficiency, i.e. lower voltages, lower energy and shorter procedure times than IRE and without the need for chemotoxic additives as in ECT. Methods: A new E2 waveform was designed that delivers optimal doses of electroporation and electrolysis in a single waveform. A series of experiments were performed in the liver of pigs to evaluate E2 in the context of clinical applications. The goal was to find initial parameter boundaries in terms of electrical field, pulse duration and charge as well as tissue behavior to enable real time tissue ablation of clinically relevant volumes. Results: Histological results show that a single several hundred millisecond long E2 waveform can ablate large volume of tissue at relatively low voltages while preserving the integrity of large blood vessels and lumen structures in the ablation zone without the use of chemotoxic drugs or paralyzing drugs during anesthesia. This could translate clinically into much shorter treatment times and ease of use compared to other techniques that are currently applied.

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“…Furthermore, the endovascular IRE has been investigated for vascular smooth muscle cells. This minimally invasive method is used for creating a suitable niche for exogenous cell engraftment in regenerative surgery [ 57 , 58 ].…”

Section: Irementioning

confidence: 99%

Electroporation-Based Treatments in Urology

Szlasa

Saczko

Kulbacka

2020

Cancers

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The observation that an application of a pulsed electric field (PEF) resulted in an increased permeability of the cell membrane has led to the discovery of the phenomenon called electroporation (EP). Depending on the parameters of the electric current and cell features, electroporation can be either reversible or irreversible. The irreversible electroporation (IRE) found its use in urology as a non-thermal ablative method of prostate and renal cancer. As its mechanism is based on the permeabilization of cell membrane phospholipids, IRE (as well as other treatments based on EP) provides selectivity sparing extracellular proteins and matrix. Reversible EP enables the transfer of genes, drugs, and small exogenous proteins. In clinical practice, reversible EP can locally increase the uptake of cytotoxic drugs such as cisplatin and bleomycin. This approach is known as electrochemotherapy (ECT). Few in vivo and in vitro trials of ECT have been performed on urological cancers. EP provides the possibility of transmission of genes across the cell membrane. As the protocols of gene electrotransfer (GET) over the last few years have improved, EP has become a well-known technique for non-viral cell transfection. GET involves DNA transfection directly to the cancer or the host skin and muscle tissue. Among urological cancers, the GET of several plasmids encoding prostate cancer antigens has been investigated in clinical trials. This review brings into discussion the underlying mechanism of EP and an overview of the latest progress and development perspectives of EP-based treatments in urology.

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Using Non-Thermal Irreversible Electroporation to create an in Vivo Niche for Exogenous Cell Engraftment

Cited by 25 publications

References 14 publications

Molecular and histological study on the effects of non-thermal irreversible electroporation on the liver

Molecular and histological study on the effects of non-thermal irreversible electroporation on the liver

Peer Review #2 of "Toward a clinical real time tissue ablation technology: combining electroporation and electrolysis (E2) (v0.2)"

Electroporation-Based Treatments in Urology

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