title: Rat liver regeneration following ablation with irreversible electroporation.
abstract: 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.
authors.affiliation: Center for Engineering in Medicine, Massachusetts General Hospital, Harvard Medical School, and Shriners Hospitals for Children in Boston, Boston, MA, United States; Porter School of Environmental Studies, Tel Aviv University, Tel Aviv, Israel.
authors.forename: Alexander
authors.initials: A
authors.lastname: Golberg
authors.affiliation: Center for Engineering in Medicine, Massachusetts General Hospital, Harvard Medical School, and Shriners Hospitals for Children in Boston, Boston, MA, United States; Department of Surgery (Surgical Laboratory), Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands.
authors.forename: Bote G
authors.initials: BG
authors.lastname: Bruinsma
authors.affiliation: Center for Engineering in Medicine, Massachusetts General Hospital, Harvard Medical School, and Shriners Hospitals for Children in Boston , Boston, MA , United States.
authors.forename: Maria
authors.initials: M
authors.lastname: Jaramillo
authors.affiliation: Center for Engineering in Medicine, Massachusetts General Hospital, Harvard Medical School, and Shriners Hospitals for Children in Boston, Boston, MA, United States; Department of Biomedical Engineering, Rutgers University, Piscataway, New Jersey, United States.
authors.forename: Martin L
authors.initials: ML
authors.lastname: Yarmush
authors.affiliation: Center for Engineering in Medicine, Massachusetts General Hospital, Harvard Medical School, and Shriners Hospitals for Children in Boston , Boston, MA , United States.
authors.forename: Basak E
authors.initials: BE
authors.lastname: Uygun
keywords: Hepatocytes; Irreversible electroporation; Liver ablation; Liver regeneration; Progenitor cells; Pulsed electric fields; Scarless regeneration
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