title: Reduced liver cell death using an alginate scaffold bandage: a novel approach for liver reconstruction after extended partial hepatectomy.
abstract: Extended partial hepatectomy may be needed in cases of large hepatic mass, and can lead to fulminant hepatic failure. Macroporous alginate scaffold is a biocompatible matrix which promotes the growth, differentiation and long-term hepatocellular function of primary hepatocytes in vitro. Our aim was to explore the ability of implanted macroporous alginate scaffolds to protect liver remnants from acute hepatic failure after extended partial hepatectomy. An 87% partial hepatectomy (PH) was performed on C57BL/6 mice to compare non-treated mice to mice in which alginate or collagen scaffolds were implanted after PH. Mice were scarified 3, 6, 24 and 48 h and 6 days following scaffold implantation and the extent of liver injury and repair was examined. Alginate scaffolds significantly increased animal survival to 60% vs. 10% in non-treated and collagen-treated mice (log rank=0.001). Mice with implanted alginate scaffolds manifested normal and prolonged aspartate aminotransferases and alanine aminotransferases serum levels as compared with the 2- to 20-fold increase in control groups (P<0.0001) accompanied with improved liver histology. Sustained normal serum albumin levels were observed in alginate-scaffold-treated mice 48 h after hepatectomy. Incorporation of BrdU-positive cells was 30% higher in the alginate-scaffold-treated group, compared with non-treated mice. Serum IL-6 levels were significantly decreased 3h post PH. Biotin-alginate scaffolds were quickly well integrated within the liver tissue. Collectively, implanted alginate scaffolds support liver remnants after extended partial hepatectomy, thus eliminating liver injury and leading to enhanced animal survival after extended partial hepatectomy.
authors.affiliation: Liver Unit, Hebrew University - Hadassah Medical Center, Jerusalem, Israel; Pediatric Gastroenterology Unit, Department of Pediatrics, Hebrew University - Hadassah Medical Center, Jerusalem, Israel. Electronic address: eyals@hadassah.org.il.
authors.forename: Eyal
authors.initials: E
authors.lastname: Shteyer
authors.affiliation: Liver Unit, Hebrew University - Hadassah Medical Center, Jerusalem, Israel.
authors.forename: Ami
authors.initials: A
authors.lastname: Ben Ya'acov
authors.affiliation: Liver Unit, Hebrew University - Hadassah Medical Center, Jerusalem, Israel.
authors.forename: Lidia
authors.initials: L
authors.lastname: Zolotaryova
authors.affiliation: Liver Unit, Hebrew University - Hadassah Medical Center, Jerusalem, Israel.
authors.forename: Avital
authors.initials: A
authors.lastname: Sinai
authors.affiliation: Liver Unit, Hebrew University - Hadassah Medical Center, Jerusalem, Israel.
authors.forename: Yoav
authors.initials: Y
authors.lastname: Lichtenstein
authors.affiliation: Department of Pathology, Hebrew University - Hadassah Medical Center, Jerusalem, Israel.
authors.forename: Orit
authors.initials: O
authors.lastname: Pappo
authors.affiliation: Avram and Stella Goldstein-Goren Department of Biotechnology Engineering, Ben-Gurion University, Beer Sheva, Israel.
authors.forename: Olga
authors.initials: O
authors.lastname: Kryukov
authors.affiliation: Avram and Stella Goldstein-Goren Department of Biotechnology Engineering, Ben-Gurion University, Beer Sheva, Israel.
authors.forename: Tsiona
authors.initials: T
authors.lastname: Elkayam
authors.affiliation: Avram and Stella Goldstein-Goren Department of Biotechnology Engineering, Ben-Gurion University, Beer Sheva, Israel; Regenerative Medicine and Stem Cell (RMSC) Research Center, Ben-Gurion University, Beer Sheva, Israel. Electronic address: scohen@bgu.ac.il.
authors.forename: Smadar
authors.initials: S
authors.lastname: Cohen
authors.affiliation: Liver Unit, Hebrew University - Hadassah Medical Center, Jerusalem, Israel.
authors.forename: Yaron
authors.initials: Y
authors.lastname: Ilan
mesh_terms: D000464:Alginates; D000818:Animals; D001458:Bandages; D001973:Bromodeoxyuridine / Q000378:metabolism; D016923:Cell Death; D020723:Glucuronic Acid; D006498:Hepatectomy; D006603:Hexuronic Acids; D015850:Interleukin-6 / Q000097:blood; D008099:Liver / Q000378:metabolism / Q000473:pathology* / Q000601:surgery; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D054457:Tissue Scaffolds
chemical_list: D000464:Alginates; D006603:Hexuronic Acids; D015850:Interleukin-6; D020723:Glucuronic Acid; D001973:Bromodeoxyuridine
keywords: Alginate scaffolds; Extended partial hepatectomy; Liver; Regeneration