Exosomes derived from human umbilical cord mesenchymal stem cells attenuate hepatic ischaemia-reperfusion injury via the let-7i-5p/Faslg axis

Figure 1 Human umbilical cord mesenchymal stem cell-derived exosomes alleviate hepatic ischaemia-reperfusion injury in mice. A: Schematic of the experimental design for the mouse model of hepatic ischaemia-reperfusion injury (HIRI). The mice were subjected to occlusion of hepatic blood flow in the left lateral lobe and left medial lobe for 1 hour followed by reperfusion. At the start of reperfusion, the mice were intravenously injected with 50 μg of human umbilical cord mesenchymal stem cell-derived exosomes (hucMSC-exos), 100 μg of hucMSC-exos, or 100 μg of hucMSC-exos treated with anti-very late antigen-4 and anti-lymphocyte function-associated antigen-1 antibodies. Phosphate-buffered saline (100 μL) was used as a control for HIRI. Liver tissue samples were collected 48 hours after HIRI induction; B: Cellular uptake of DiI-labelled hucMSC-exos in liver tissue. Scale bars: 100 μm; C: TUNEL staining. Scale bars: 50 μm; D: Hematoxylin and eosin staining. Scale bars are 200 μm (top panel) and 100 μm (bottom panel); E: Western blot analysis of apoptosis-related proteins in liver tissues. I/R: Ischaemia/reperfusion; hucMSC-exos: Human umbilical cord mesenchymal stem cell-derived exosomes; LFA-1: Lymphocyte function-associated antigen-1; VLA-4: Very late antigen-4; PBS: Phosphate-buffered saline; DiI: 1,1′-dioctadecyl-3,3,3′,3′-tetramethylindocarbocyanine perchlorate; DAPI: 4’,6-diamidino-2-phenylindole; TUNEL: Terminal deoxynucleotidyl transferase-mediated dUTP nick end labelling; Bax: B-cell lymphoma-2-associated X protein; Bcl-2: B-cell lymphoma-2; Caspase-3: Cysteinyl aspartate specific proteinase-3. ^aP < 0.05, ^bP < 0.01, ^cP < 0.001, and ^dP < 0.0001.