Rat liver regeneration following ablation with irreversible electroporation

被引:31
作者
Golberg, Alexander [1 ,2 ,3 ]
Bruinsma, Bote G. [1 ,2 ,4 ]
Jaramillo, Maria [1 ,2 ]
Yarmush, Martin L. [1 ,2 ,5 ]
Uygun, Basak E. [1 ,2 ]
机构
[1] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Ctr Engn Med, Boston, MA USA
[2] Shriners Hosp Children, Boston, MA USA
[3] Tel Aviv Univ, Porter Sch Environm Studies, IL-69978 Tel Aviv, Israel
[4] Univ Amsterdam, Acad Med Ctr, Dept Surg, Surg Lab, NL-1105 AZ Amsterdam, Netherlands
[5] Rutgers State Univ, Dept Biomed Engn, Piscataway, NJ USA
关键词
Liver regeneration; Irreversible electroporation; Liver ablation; Pulsed electric fields; Scarless regeneration; Progenitor cells; Hepatocytes; PULSED ELECTRIC-FIELDS; STEM-CELLS; GROWTH-FACTORS; ADULT-RAT; PROGENITORS; EXPRESSION; PROLIFERATION; COMPARTMENT; CHALLENGES; CYTOKINES;
D O I
10.7717/peerj.1571
中图分类号
O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];
学科分类号
07 ; 0710 ; 09 ;
摘要
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 naive extracellular matrix is decellularized in vivo with completely preserved extracellular architecture.
引用
收藏
页数:17
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