Rat liver regeneration following ablation with irreversible electroporation
Open accessAbstract
During the past decade, irreversible electroporation (IRE) ablation has emerged as a promising tool for the treatment of multiple diseases including hepatic cancer. However, the mechanisms behind the tissue regeneration following IRE ablation have not been investigated. Our results indicate that IRE treatment immediately kills the cells at the treatment site preserving the extracellular architecture, in effect causing in vivo decellularization. Over the course of 4 weeks, progenitor cell differentiation, through YAP and notch pathways, together with hepatocyte expansion led to almost complete regeneration of the ablated liver leading to the formation of hepatocyte like cells at the ablated zone. We did not observe significant scarring or tumor formation at the regenerated areas 6 months post IRE. Our study suggests a new model to study the regeneration of liver when the naïve extracellular matrix is decellularized in vivo with completely preserved extracellular architecture.
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Golberg et al. successfully decellularized different zones of the rat liver in vivo by applying 90 unipolar, rectangular electric 70 μs pulses, at 150 Vmm−1 potential difference between the electrodes, at 4 Hz.
“Golberg et al. successfully decellularized different zones of the rat liver in vivo by applying 90 unipolar, rectangular electric 70 μs pulses, at 150 Vmm−1 potential difference between the electrodes, at 4 Hz [140].”
From Liver tissue engineering using decellularized scaffolds: Current progress, challenges, and opportunities (2024) · cites this paper as [140]
The Results section reports rapid decellularization in treated rat liver lobes. But Materials and Methods identifies the quoted 90-pulse, 70 μs, 150 V/mm settings as a protocol from previous work (Golberg et al., 2011), not the protocol used for this study; this study used 99 pulses of 50 μs at 360 V across 3 mm. (LLM, conf=0.91)
Experimental — accuracy not yet measuredThe treated areas showed rapid decellularization with preservation of the ECM structure.
“The treated areas showed rapid decellularization with preservation of the ECM structure.”
From Liver tissue engineering using decellularized scaffolds: Current progress, challenges, and opportunities (2024) · cites this paper as [140]
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Hussein, K. H., Ahmadzada, B., Correa, J. C., Sultan, A., Wilken, S., Amiot, B., & Nyberg, S. L. (2024) · Bioactive Materials · doi:10.1016/j.bioactmat.2024.06.001 · Cited by 28 · see citing works
“This technique has been utilized for tissue and organ decellula-rization, including blood vessels, myocardium, and liver, both in vitro and in vivo [140 – 144].”
Method
- Authors
- Golberg, A., Bruinsma, B. G., Jaramillo, M., Yarmush, M. L., & Uygun, B. E.
- Affiliations
- Harvard University (US)
- Center for Engineering in Medicine, Massachusetts General Hospital, Harvard Medical School, and Shriners Hospitals for Children in Boston, Boston, MA, United States
- Rutgers, The State University of New Jersey (US)
- Corresponding author
- Golberg, Alexander
- Uygun, Basak E.
- Venue
- PeerJ
- Publisher
- PeerJ
- Published
- 2016-01-21
- Volume
- 4
- Pages
- e1571
- ISSN
- 2167-8359 (ISSN-L)
- PMC
- PMC4727979
- OpenAlex
- W2252515784
- Cited by
- 38
- References
- 3
- Citations by year
- 2026: 1 · 2025: 3 · 2024: 1 · 2023: 3 · 2022: 4 · 2021: 5 · 2020: 7 · 2019: 4 · 2018: 4 · 2017: 5 · 2016: 1
- FWCI
- 3.38
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Locations
- PeerJ (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- Data Archiving and Networked Services (DANS) (submittedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- Funders
- Claflin Distinguished Scholar Award from Massachusetts General Hospital (2013A050726)
- Topics
- Health Sciences › Medicine › Hepatology › Liver physiology and pathology
- Health Sciences › Medicine › Surgery › Tissue Engineering and Regenerative Medicine
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Biotechnology › Microbial Inactivation Methods
- Keywords
- irreversible electroporation, liver regeneration, decellularization, extracellular matrix, hepatic progenitor cells, YAP signaling, Notch signaling, hepatocyte differentiation, hepatocyte-like cells, rat liver, tissue ablation
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