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Therapeutic effects of mesenchymal stem cells-conditioned medium derived from suspension cultivation or silymarin on liver failure mice

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Abstract

Background

Common treatments of liver disease failed to meet all the needs in this important medical field. It results in an urgent need for proper some new adjuvant therapies. Mesenchymal stem cells (MSCs) and their derivatives are promising tools in this regard. We aimed to compare the Silymarin, as traditional treatment with mesenchymal stem cell conditioned medium (MSC-CM), as a novel strategy, both with therapeutic potentialities in term of liver failure (LF) treatment.

Methods and results

Mice models with liver failure were induced with CCl4 and were treated in the groups as follows: normal mice receiving DMEM-LG medium as control, LF-mice receiving DMEM-LG medium as sham, LF-mice receiving Silymarin as LF-SM, and LF-mice receiving MSC sphere CM as LF-MSC-CM. Biochemical, histopathological, molecular and protein level parameters were evaluated using blood and liver samples. Liver enzymes, MicroRNA-122 values as well as necrotic score were significantly lower in the LF-SM and LF-MSC-CM groups compared to sham. LF-SM showed significantly higher level of total antioxidant capacity and malondialdehyde than that of LF-MSC-CM groups. Sph-MSC-CM not only induced more down-regulated expression of fibrinogen-like protein 1 and receptor interacting protein kinases1 but also led to higher expression level of keratinocyte growth factor. LF-MSC-CM showed less mortality rate compared to other groups.

Conclusions

Hepato-protective potentialities of Sph-MSC-CM are comparable to those of Silymarin. More inhibition of necroptosis/ necrosis and inflammation might result in rapid liver repair in case of MSC-CM administration.

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Acknowledgements

This work was supported by Hamadan university of medical sciences financially (No: 990202405, Ethic code No: IR.UMSHA.REC.1398.1077). Special thanks to high institute for research and education in transfusion medicine, Tehran, Iran for technical supports.

Funding

This work was supported by Hamadan university of medical sciences financially (No: 990202405).

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Authors and Affiliations

  1. Social Determinants of Health Research Center, Saveh University of Medical Sciences, Saveh, Iran

    Sedigheh Molaei

  2. Department of Medical Laboratory Sciences, School of Para Medicine, Hamadan University of Medical Sciences, Hamadan, Iran

    Fatemeh Amiri

  3. Department of Emergency Medicine, Besat Hospital, Hamadan University of Medical Sciences, Hamadan, Iran

    Rasoul Salimi

  4. Blood Transfusion Research Center, High Institute for Research and Education in Transfusion Medicine, Tehran, Iran

    Shirin Ferdowsi & Marzie Bahadori

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  1. Sedigheh Molaei
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  2. Fatemeh Amiri
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Contributions

Conceptualization: FA, Methodology: SM, SF and MB, Formal analysis: RS, Investigation and Writing—original draft preparation: SM and MB, Review and editing: FA, MB and SF, Funding acquisition: FA, RS, Supervision: FA.

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Correspondence to Fatemeh Amiri.

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Conflict of interest

The authors declare that they have no conflict of interest.

Ethical approval

All procedures were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards. Informed consent: MSCs were isolated from human umbilical cord samples after filling out the consent form by parents.

Research involving human and animal rights

All applicable international, national, and/or institutional guidelines for the care and use of animals were followed. This study was confirmed in ethic committee of Hamadan university of medical sciences (Code No: IR.UMSHA.REC.1398.1077).

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Molaei, S., Amiri, F., Salimi, R. et al. Therapeutic effects of mesenchymal stem cells-conditioned medium derived from suspension cultivation or silymarin on liver failure mice. Mol Biol Rep 49, 10315–10325 (2022). https://doi.org/10.1007/s11033-022-07785-4

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