| Liver is the key organ of the human body’s metabolism and energy conversion. The liver has strong regeneration ability, after acute、chronic trauma and a variety of liver surgery, remnant liver will enter the fast and complex regeneration. Faster and more effectively regeneration of liver cells to compensate for impaired liver function is still the clinical problems to face. Previous studies have shown that mesenchymal stem cells(mesenchymal stem cell, MSC) which are similar to other stem cells also have the multiple differentiation potential,and because of its low immunity, as an important means of treatment of brain, heart, kidney and liver damage and repair. However, at present, more and more experiments confirmed, stem cells on the repair of tissue injury is the main mechanism is the intervention of the production and secretion of bioactive factors on the damage of cell metabolism. Exosome is the most value factor in the these bioactive factors.In early course of the study, we use the Hi PSC-MSCs derived exosome on hepatic ischemia and reperfusion model in rats. The results show that the Hi PSC-MSCs-Exo reduce ischemia and reperfusion induced liver injury, and promote the repair of liver injury, but whether Hi PSC-MSCs-Exo can promote liver regeneration and repair after liver resection is not clear.Objectlve: To explore the effects of exosomes released from human induced pluripotent stem cells-derived MSC(Hi PSC-MSCs-Exo) on liver regeneration and repair after partial hepatectomy.Methods: Exosome was extracted from Hi PSC-MSCs and observed under transmission electron microscope.The expression of surface molecular marker CD9、CD63、CD81was tested by western blot. The model of 70% hepatectomy was established with rats.Male Sprague.Dawley rats were randomly grouped into hepatectomy,Hi PSC-MSC derived exosome treated groups.The histomorphological changes in of liver tissue samples were examined by hematoxylin and eosin-stained tissue samples.The liver functions were tested by biochemical methods. The TNF-a and IL-6 were tested by elisa methods. The flow cytometry and immunohistochemistry were used to detect the hepatocyte cell cycle and proliferation cell nuclear antigen(PCNA)Results: Hi PSC-MSCs were isolated、cultured and identified.MSC differentiatedsuccessfully into osteoblasts and lipocytes after growing in osteoblast- and lipocpeinducing media.Exosome were isolated,Dectection of surface markers revealed high expression levels of CD9、CD63、CD81. The liver tissues displayed that hepatic sinusoid mild expansion, less inflammatory cell infiltration and rare necrotic lesions after 1d, and 3d operation, in the experimental group than those of the control group. The levels of aspartate aminotransferase(ALT) and aspartate aminotransferase(AST) were decreased more significantly in experimental group than those in control group(P < 0.05). The TNF-a and IL-6 levels in contorl group were higher than those in experimental group after 1d and 3d operation(P<0.05). The S phase of hepatocyte cell cycle was significantly higher in experimental group than those in control group(P < 0.05).The remnant liver immunohistochemistry showed that PCNA expression was significantly higher in the experimental group after 1d、3d、5d and 7d operation than that in the control group(P < 0.05).Conclusion: Hi PSC-MSCs-Exo can reduce the damage of liver tissue,also can improve liver function and promote liver regeneration after 70% hepatectomy. |
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