Adult-Derived Human Liver Stem/Progenitor Cells Infused 3 Days Postsurgery Improve Liver Regeneration in a Mouse Model of Extended Hepatectomy. Issue 2 (February 2017)

• Record Type: Journal Article
• Authors: Herrero, Astrid; Prigent, Julie; Lombard, Catherine; Rosseels, Valérie; Daujat-Chavanieu, Martine; Breckpot, Karine; Najimi, Mustapha; Deblandre, Gisèle; Sokal, Etienne M.
• Is Part Of: Cell transplantation. Volume 26:Issue 2(2017)
• Page Start: 351
• Page End: 364
• Publication Date: 2017-02
• Subjects: Hepatic stem/progenitor cells -- Mesenchymal cells -- Xenotransplantation -- Liver failure -- Engraftment -- Alu qPCR; Cell transplantation -- Periodicals; Cell Transplantation; Cell transplantation; Electronic journals; Periodicals; Periodicals; 571.638
• DOI: 10.3727/096368916X692960
• Languages: English
• ISSNs: 0963-6897

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 −/- IL2R g -/- ) 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.