HNF4α overexpression enhances the therapeutic potential of umbilical cord mesenchymal stem/stromal cells in mice with acute liver failure.
Yeping YuQiqi ZhangNing WuLei XiaJie CaoQiang XiaJie ZhaoJianjun ZhangHua Lian HangPublished in: FEBS letters (2022)
Human umbilical cord mesenchymal stem/stromal cells (hUMSCs) hold promise for treating acute liver failure (ALF). Here, we investigated the therapeutic effect of hUMSCs overexpressing hepatocyte nuclear factor 4α (HNF4α), a transcription factor important for maintaining hepatocyte identity and hepatic functions, in ALF, compared with hUMSCs without overexpression of HNF4α (CON-hUMSCs). The cells were administered into mice via the tail vein for 24 h before exposure to lipopolysaccharide/d-galactosamine (LPS/d-GalN) for 6 h by intraperitoneal injection. HNF4α-hUMSCs ameliorated liver injury in ALF better than CON-hUMSCs. The overexpression of HNF4α enhanced the transcription of interleukin (IL)-10 and promoted M2 macrophage polarization through the IL-10/signal transducer and activator of transcription 3 (STAT3) pathway. HNF4α-hUMSCs could exert a more pronounced therapeutic effect on ALF than CON-hUMSCs, providing a novel therapy for ALF.
Keyphrases
- liver failure
- nuclear factor
- liver injury
- umbilical cord
- drug induced
- transcription factor
- toll like receptor
- mesenchymal stem cells
- hepatitis b virus
- cell proliferation
- inflammatory response
- bone marrow
- stem cells
- immune response
- induced apoptosis
- dna binding
- type diabetes
- respiratory failure
- lps induced
- deep learning
- metabolic syndrome
- endoplasmic reticulum stress
- high resolution
- ultrasound guided
- single molecule
- wild type
- mechanical ventilation
- pluripotent stem cells