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Cited by 9Mesenchymal stem cell researchLiver physiology and pathologyLiver Disease and Transplantation

Pretreatment of UC-MSCs with IFN-α2 improves treatment of liver fibrosis by recruiting neutrophils

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Xie, Ye, Yao, Jia, Yan, Mengchao, Lin, Yan, Wei, Jiayun, Wang, Haiping, Mao, Yongcui, Liu, Pinyan +1 more·2023·Journal of Translational Medicine
DOI 10.1186/s12967-023-04732-0PMC PMC10656886
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Abstract

Background: The use of umbilical cord mesenchymal stem cells (UC-MSCs) is a burgeoning method for the treatment of liver cirrhosis. However, the secretory phenotype and regulatory ability of UC-MSCs are easily affected by their microenvironment. Ensuring a specific microenvironment to enhance the UC-MSCs phenotype is a potential strategy for improving their therapeutic efficacy. The aim of this study was to explore therapeutic UC-MSCs phenotypes for improving liver fibrosis. Methods: RNA-sequencing was used to analyze the response pattern of UC-MSCs after exposure to the serum of cirrhotic patients with HBV. Using immunohistochemistry, quantitative polymerase chain reaction, and immunofluorescence techniques, we evaluated the therapeutic effect of UC-MSCs pretreated with interferon alpha 2 (IFN-α2) (pre-MSCs) in an animal model of cirrhosis. Immunoblotting, ELISA, and other techniques were used to analyze the signaling pathways underlying the IFN-induced changes in UC-MSCs. Results: UC-MSCs exposed to the serum of patients with hepatitis B-induced cirrhosis showed an enhanced response to type I IFN. The activated type I IFN signal induced the highest secretion of colony-stimulating factor 3 (CSF-3), interleukin (IL)-8, and chemokine (C–C motif) ligand 20 (CCL20) by the UC-MSCs. Pre-MSCs showed a higher therapeutic efficacy than untreated UC-MSCs in an animal model of liver fibrosis. Immunohistochemical analysis revealed that pre-MSCs could recruit neutrophils resulting in an increase in the secretion of matrix metalloprotease 8 that alleviated fibrosis. When neutrophils in animals were depleted, the therapeutic effect of pre-MSCs on fibrosis was inhibited. IFN-α2 altered the secretory phenotype of UC-MSCs by activating phosphorylated signal transducer and activator of transcription 1 and 2 (p-STAT1 and p-STAT2). Conclusions: Pre-MSCs exhibited enhanced secretion of CSF-3, IL-8, and CCL20 and recruited neutrophils to alleviate fibrosis. This new strategy can improve cell therapy for liver cirrhosis. Graphical abstract:

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  • Priming MSCs or MSC-CM with IFN-γ, TNF-α, IL-1β, or IFN-α2 increases their anti-inflammatory and anti-fibrotic effects.

    “It has been demonstrated that IFN-γ, TNF-α, IL-1β, or IFN-α2-primed MSCs or MSC-CM have increased anti-inflammatory and anti-fibrotic effects [349–351].”

    From Mechanisms, efficacy, and future perspectives of cellular-based therapies for liver fibrosis/cirrhosis: focusing on mesenchymal stromal cells (2025) · cites this paper as [350]

    The Results section (“Pretreatment of UC-MSCs with IFN-α2 can improve their therapeutic effect”; page unavailable) reports less collagen deposition with IFN-α2-pretreated UC-MSCs than with untreated MSCs in rats with liver fibrosis. This supports the anti-fibrotic part for IFN-α2-primed cells. The paper does not establish increased anti-inflammatory effects or test primed MSC-conditioned medium; it does not establish the claimed effects for the other listed priming agents. (LLM, conf=0.86)

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Cited by

Sorted by citations

Authors
Xie, Y., Yao, J., Yan, M., Lin, Y., Wei, J., Wang, H., Mao, Y., Liu, P., & Li, X.
Affiliations
  • Lanzhou University (CN)
  • First Hospital of Lanzhou University (CN)
Corresponding author
Li, Xun
ORCID
Venue
Journal of Translational Medicine
Publisher
Springer Science and Business Media LLC
Published
2023-11-18
Volume
21
Issue
1
Pages
832-832
ISSN
1479-5876 (ISSN-L)
DOI
10.1186/s12967-023-04732-0
PMC
PMC10656886
OpenAlex
W4388796486
Cited by
9
References
11
Citations by year
2026: 2 · 2025: 4 · 2024: 3
FWCI
1.56
Type
journal article
Language
en
Open access
Licence
Locations
  • Journal of Translational Medicine (publishedVersion, cc-by)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
Funders
  • National Natural Science Foundation of China (82060119, 32160230)
  • Fundamental Research Funds for the Central Universities (lzujbky-2021-kb37)
Topics
  • Health Sciences › Medicine › Genetics › Mesenchymal stem cell research
  • Health Sciences › Medicine › Hepatology › Liver physiology and pathology
  • Health Sciences › Medicine › Hepatology › Liver Disease and Transplantation
Keywords
human umbilical cord mesenchymal stem cells, interferon alpha 2, liver fibrosis, liver cirrhosis, neutrophil recruitment, type I interferon signaling, interleukin-8, CCL20, matrix metalloproteinase-8, cell therapy, secretory phenotype
MeSH terms
Interferon alpha-2, Animals, Fibrosis, Humans, Liver Cirrhosis, Neutrophils, Umbilical Cord, Mesenchymal Stem Cell Transplantation, Mesenchymal Stem Cells

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