Effects of human umbilical cord mesenchymal stem cells-derived exosomes on liver regeneration

Objective To investigate whether human umbilical cord mesenchymal stem cells-derived exosomes (hucMSC-Ex) could promote liver regeneration after major hepatoectomy in mice and hepatocytes proliferation. Methods Using models of 2/3 partial hepatectomy in mice, we evaluated whether hucMSCs-Ex promoted liver regeneration in vivo. Remnant liver to body weight ratio, liver function, hematoxylin and eosin (HE) stain and proliferation cell nuclear antigen (Ki-67) immunohistochemistry of remnant liver tissue were analyzed 24, 48 and 72 h after surgery. Cell counting kit 8 was used to evaluate whether hucMSC-Ex induced hepatocytes proliferation in vitro. Results Exosomes ranging from 50-150 nm were isolated frome hucMSCs conditioned medium using differential centrifugation. Western blotting analysis of exosomes showed positive expression of CD63, CD9, and HSP90α. Remnant liver to body weight ratio was significantly increased 48 h and 72 h after hepatectomy in mice injected with hucMSC-Ex as compared with the PBS control group [(3.06±0.44)% vs. (2.67±0.23)%, and (3.18±0.29)% vs. (2.75±0.24)%, P=0.047, 0.013]. Serum alanine aminotransferase (ALT) [(165.0±29.7) vs. (1 596.0±711.9) U/L, and (49.5±18.7) vs. (124.0±39.7) U/L] and aspartate aminotransferase (AST) [(285.0±31.1) vs. (3 030.0±1 249.0) U/L, and (126.3±29.6) vs. (198.3±37.3) U/L] was significantly lower in exosomes group than in control group (P=0.014, 0.014, 0.011, and 0.030 respectively). Besides, less pathological changes were observed after administration of hucMSC-Ex. Increased Ki-67 positive cells 24, 48 and 72 h after hepatectomy were shown in exosomes group compared to PBS control.In vitro study, proliferation of hepatocytes was significantly increased in exosomes (100 μg/ml) group (1.198±0.087 vs. 0.970±0.032, P=0.006). Conclusion HucMSC-Ex could promote hepatocyte proliferation and liver regeneration after hepatectomy, but the mechanisms are still neededed to be elucidated. Key words: Mesenchymal stem cells; Exosomes; Liver regeneration; Hepatectomy