BACKGROUND: In this study we investigated whether adipose-derived stem cells (ADSCs) had any beneficial protective effects on liver injury and regeneration in vivo. Moreover, we examined whether ADSCs protect hepatocytes via trophic molecules. MATERIALS AND METHODS: We transplanted ADSCs into mice after 70% hepatectomy and ischemia-reperfusion, and observed liver injury and regeneration after reperfusion. We co-cultured hepatocytes with ADSCs using a Transwell system for 7 d and evaluated the viabilities of hepatocytes and the cytokine levels in the culture medium. Bevacizumab was used to confirm the effect of vascular endothelial growth factor (VEGF) on hepatocytes. RESULTS: ADSCs improved serum liver function at 6 h after reperfusion in a nonlethal model and stimulated liver regeneration at 24 h after reperfusion in a lethal model. VEGF levels in the culture medium were increased by co-culture ADSCs with hepatocytes. ADSCs improved the viabilities of hepatocytes. The inhibited production of VEGF by bevacizumab did not affect the viability of hepatocytes. CONCLUSIONS: ADSCs were able to ameliorate liver injury and stimulate liver regeneration in subsequent hepatectomy and ischemia-reperfusion-injured model mice. Furthermore, hepatocytes were protected by the trophic molecules of the ADSCs. However, such protective effects might be provided by mechanisms other than VEGF signaling.
BACKGROUND: In this study we investigated whether adipose-derived stem cells (ADSCs) had any beneficial protective effects on liver injury and regeneration in vivo. Moreover, we examined whether ADSCs protect hepatocytes via trophic molecules. MATERIALS AND METHODS: We transplanted ADSCs into mice after 70% hepatectomy and ischemia-reperfusion, and observed liver injury and regeneration after reperfusion. We co-cultured hepatocytes with ADSCs using a Transwell system for 7 d and evaluated the viabilities of hepatocytes and the cytokine levels in the culture medium. Bevacizumab was used to confirm the effect of vascular endothelial growth factor (VEGF) on hepatocytes. RESULTS: ADSCs improved serum liver function at 6 h after reperfusion in a nonlethal model and stimulated liver regeneration at 24 h after reperfusion in a lethal model. VEGF levels in the culture medium were increased by co-culture ADSCs with hepatocytes. ADSCs improved the viabilities of hepatocytes. The inhibited production of VEGF by bevacizumab did not affect the viability of hepatocytes. CONCLUSIONS: ADSCs were able to ameliorate liver injury and stimulate liver regeneration in subsequent hepatectomy and ischemia-reperfusion-injured model mice. Furthermore, hepatocytes were protected by the trophic molecules of the ADSCs. However, such protective effects might be provided by mechanisms other than VEGF signaling.
Authors: Ioannis G Papanikolaou; Charalambos Katselis; Konstantinos Apostolou; Themistoklis Feretis; Maria Lymperi; Manousos M Konstadoulakis; Apostolos E Papalois; George C Zografos Journal: Stem Cells Int Date: 2017-03-13 Impact factor: 5.443