Adult-derived human liver stem/progenitor cells infused 3 days post-surgery improve liver regeneration in a mouse model of extended hepatectomy.
(2017) Cell Transplantation — Vol. 26, n° 2, p. 351-364 (2017)
Files
Adult-derivedhumanliverstemprogenitorcellsinfused3dayspost-surgeryimproveliverregenerationinamousemodelofextendedhepatectomy.pdf
Restricted Access - Adobe PDF
- 445.22 KB
Details
- Authors
- 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 human liver mesenchymal stem/progenitor cells (ADHLSCs) at two different early time points in an immunodeficient mouse model (Rag(2-/-)IL2Rγ(-/-) ) that had undergone a 70%-hepatectomy procedure. The hepato-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 alpha-smooth muscle actin. In addition, cell proliferation (anti-mouse and human Ki67 staining) and murine liver weight were measured in order to evaluate liver regeneration. At Day 1 post-transplantation, the ratio of human to mouse cells was similar in both groups, whereas 1 week post-transplantation, this ratio was significantly improved (p <0.016) in mice receiving ADHLSC injection at Day 3 post-hepatectomy (1.7%), compared to those injected at the time of surgery (1%). Based on liver weight, mouse liver regeneration was more extensive 1 week post-transplantation 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.
- Affiliations
Citations
Herrero, A., Prigent, J., Lombard, C., Rosseels, V., Daujat-Chavanieu, M., Breckpot, K., Najimi, M., Deblandre, G., & Sokal, E. (2017). Adult-derived human liver stem/progenitor cells infused 3 days post-surgery improve liver regeneration in a mouse model of extended hepatectomy. Cell Transplantation, 26(2), 351-364. https://doi.org/10.3727/096368916X692960 (Original work published 2017)