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. 2023 May 12;28:50–60. doi: 10.1016/j.bioactmat.2023.04.024

Fig. 5.

Fig. 5

In vivo therapeutic efficiency of TDN-miR122-hMSCs on ALF mice. (A) Schematic diagram of the experimental procedure. Intravenous injection (I.V.), Intraperitoneal injection (I.P.). (B–D) Digital photos of major organs from ALF mice after various treatments at the end of the experiment (I: undifferentiated hMSCs, II: TDN treated hMSCs, III: miR122 treated hMSCs, IV: TDN-miR122 treated hMSCs, V: free-TDN, VI: TDN + TDN-miR122 treated hMSCs). (E) In vivo fluorescence biodistribution images of various tissues (hearts, livers, spleens, lungs and kidneys) at 3 days after intravenous injection of the DiD labeled different cells. (F) The whole liver scanning distribution image of TDN-miR122-hMSCs group and TDN-miR122-hMSCs combined with TDN treatment group, cells were labeled with DiD dye (scale bar: 1 mm). (G) Quantitative real-time PCR (qRT-PCR) was used to measure human Alu-sequences specificity (the most conserved region in human DNA) for the identification and quantification of human cell lines (rose red: ALF, blue: hMSCs, orange: TDN treated hMSCs, green: miR122 treated hMSCs, pink: TDN-miR122 treated hMSCs, dark green: free-TDN, purple: TDN + TDN-miR122 treated hMSCs). (H) Immunofluorescent staining of hepatocyte marker human HNF4α expression in liver tissue of TDN-miR122-hMSCs groups and TDN-miR122-hMSCs with TDN added treatment group (scale bar: 100 μm). (I) H&E stain (N, necrosis), Ki67-positive cells (red nuclei) and TUNEL-positive cells (red nuclei), TNF-α and ROS concentrations (Scale bar: 50 μm) of the liver tissues from ALF mice treated with different groups on day 3 (Scale bar: 100 μm) (I: undifferentiated hMSCs, II: TDN treated hMSCs, III: miR122 treated hMSCs, IV: TDN-miR122 treated hMSCs, V: free-TDN, VI: TDN + TDN-miR122 treated hMSCs). (J) Analysis of hematological markers of liver damage (Normal range (blue background). ALT, alanine aminotransferase; AST, aspartate aminotransferase in the ALF mice after different treatments. (K) The detection of urea nitrogen (UN) in the serum of mice after various treatments.