title: Adult-Derived Human Liver Stem/Progenitor Cells Infused 3 Days Postsurgery Improve Liver Regeneration in a Mouse Model of Extended Hepatectomy.
abstract: There is growing evidence that cell therapy constitutes a promising strategy for liver regenerative medicine. In the setting of hepatic cancer treatments, cell therapy could prove a useful therapeutic approach for managing the acute liver failure that occurs following extended hepatectomy. In this study, we examined the influence of delivering adult-derived human liver stem/progenitor cells (ADHLSCs) at two different early time points in an immunodeficient mouse model (Rag2-/-IL2Rγ-/-) that had undergone a 70% hepatectomy procedure. The hepatic mesenchymal cells were intrasplenically infused either immediately after surgery (n = 26) or following a critical 3-day period (n = 26). We evaluated the cells' capacity to engraft at day 1 and day 7 following transplantation by means of human Alu qPCR quantification, along with histological assessment of human albumin and α-smooth muscle actin. In addition, cell proliferation (anti-mouse and human Ki-67 staining) and murine liver weight were measured in order to evaluate liver regeneration. At day 1 posttransplantation, the ratio of human to mouse cells was similar in both groups, whereas 1 week posttransplantation this ratio was significantly improved (p < 0.016) in mice receiving ADHLSC injection at day 3 posthepatectomy (1.7%), compared to those injected at the time of surgery (1%). On the basis of liver weight, mouse liver regeneration was more extensive 1 week posttransplantation in mice transplanted with ADHLSCs (+65.3%) compared to that of mice from the sham vehicle group (+42.7%). In conclusion, infusing ADHLSCs 3 days after extensive hepatectomy improves the cell engraftment and murine hepatic tissue regeneration, thereby confirming that ADHLSCs could be a promising cell source for liver cell therapy and hepatic tissue repair.
authors.forename: Astrid
authors.initials: A
authors.lastname: Herrero
authors.forename: Julie
authors.initials: J
authors.lastname: Prigent
authors.forename: Catherine
authors.initials: C
authors.lastname: Lombard
authors.forename: Valérie
authors.initials: V
authors.lastname: Rosseels
authors.forename: Martine
authors.initials: M
authors.lastname: Daujat-Chavanieu
authors.forename: Karine
authors.initials: K
authors.lastname: Breckpot
authors.forename: Mustapha
authors.initials: M
authors.lastname: Najimi
authors.forename: Gisèle
authors.initials: G
authors.lastname: Deblandre
authors.forename: Etienne M
authors.initials: EM
authors.lastname: Sokal
mesh_terms: D000410:Alanine Transaminase / Q000097:blood; D000818:Animals; D001219:Aspartate Aminotransferases / Q000097:blood; D049109:Cell Proliferation / Q000502:physiology; D004195:Disease Models, Animal; D006498:Hepatectomy; D022781:Hepatocytes / Q000166:cytology / Q000378:metabolism; D006801:Humans; D008099:Liver / Q000166:cytology* / Q000473:pathology / Q000601:surgery; D008107:Liver Diseases / Q000097:blood / Q000378:metabolism / Q000601:surgery / Q000628:therapy; D008115:Liver Regeneration / Q000502:physiology; D008297:Male; D045164:Mesenchymal Stem Cell Transplantation; D008648:Mesoderm / Q000166:cytology / Q000378:metabolism; D051379:Mice; D008822:Mice, Transgenic; D013234:Stem Cells / Q000166:cytology* / Q000502:physiology*
chemical_list: D001219:Aspartate Aminotransferases; D000410:Alanine Transaminase