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HNF4α overexpression enhances the therapeutic potential of umbilical cord mesenchymal stem/stromal cells in mice with acute liver failure
Author(s) -
Yu Yeping,
Zhang Qiqi,
Wu Ning,
Xia Lei,
Cao Jie,
Xia Qiang,
Zhao Jie,
Zhang Jianjun,
Hang Hualian
Publication year - 2022
Publication title -
febs letters
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.593
H-Index - 257
eISSN - 1873-3468
pISSN - 0014-5793
DOI - 10.1002/1873-3468.14453
Subject(s) - mesenchymal stem cell , stat3 , hepatocyte nuclear factor 4 , umbilical cord , stem cell , chemistry , stat protein , stromal cell , cancer research , immunology , microbiology and biotechnology , medicine , transcription factor , signal transduction , biology , biochemistry , gene , nuclear receptor
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.