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Intra-tracheal delivery of mesenchymal stem cell-conditioned medium ameliorates pathological changes by inhibiting apoptosis in asthmatic rats

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Abstract

Background

Asthma, an inflammatory illness of the lungs, remains the most common long-term disease amongst children. This study tried to elaborate the status of apoptosis in asthmatic pulmonary niche after the application of rat mesenchymal stem cells (MSC-CM)-derived secretome.

Methods and results

Here, we randomly allocated male Wistar rats into three groups (n = 8); Control animals were intratracheally given 50 μl vehicle. In control-matched sensitized rats, 50 μl normal saline was used. In the last group, 50 μl MSC-CM was applied. Two-week post-administration, transcription of T-bet, GATA-3, Bax, Bcl-2 and Caspase-3 was measured by gene expression analysis. Pathological injuries were monitored using H&E staining. The BALF level of TNF-α was measured using ELISA assay. In asthmatic rats received MSC-CM, the expression of T-bet was increased while the level of GATA-3 decreased compared to the S group (p < 0.05). Levels of BALF TNF-α were suppressed in asthmatic niche after MSC-CM administration (p < 0.05). Compared to the asthmatic group, MSC-CM had potential to alter the expression of apoptosis-related genes in which the expression of Bax and Caspase 3 was decreased and the expression of pro-survival factor, Bcl-2 increased (p < 0.05).

Conclusion

Our data notified the potency of direct administration of MSC-CM in the alleviation of airway inflammation, presumably by down regulating apoptotic death in pulmonary niche.

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Acknowledgements

Authors wish to thank the personnel Drug Applied Research Center of Tabriz University of medical sciences for guidance and help.

Funding

The present study received a grant from Tabriz University of Medical Sciences (No: TBZMED. REC.1399.069).

Author information

Authors and Affiliations

  1. Drug Applied Research Center, Tabriz University of Medical Sciences, Tabriz, Iran

    Rana Keyhanmanesh

  2. Department of Physiology, Faculty of Medicine, Tabriz University of Medical Sciences, Tabriz, Iran

    Fatemeh Khodamoradi

  3. Stem Cell Research Center, Tabriz University of Medical Sciences, Tabriz, Iran

    Reza Rahbarghazi, Afshin Rahbarghazi, Mahdi Ahmadi, Leila Salimi & Aref Delkhosh

  4. Department of Applied Cell Sciences, Faculty of Advanced Medical Sciences, Tabriz University of Medical Sciences, Tabriz, Iran

    Reza Rahbarghazi

  5. Solid Tumor Research Center, Cellular and Molecular Medicine Institute, Urmia University of Medical Sciences, Urmia, Iran

    Jafar Rezaie

Authors
  1. Rana Keyhanmanesh
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  3. Reza Rahbarghazi
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  6. Mahdi Ahmadi
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Contributions

RK, FM and HH performed rat model of asthma and sampling, HSB, SS, AR and HR performed ELISA and real-time PCR analysis; RR, AD and YB did the pathological examination and IF imaging; MA supervised the study. All authors approved the manuscript. All authors have seen and approved the final version of the manuscript being submitted. We warrant that the article is the authors’ original work, and it hasn’t received prior publication and isn’t under consideration for publication elsewhere.

Corresponding author

Correspondence to Mahdi Ahmadi.

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Conflict of interest

The authors declare no competing interests.

Ethical approval

The study received approval from Ethical Committee of Tabriz University of Medical Sciences (No: TBZMED. REC.1399.069). Animal care and handling procedures were conducted in accordance with the guideline for the Care and Use of Laboratory Animals (National Institutes of Health, publication no 85‐23, revised 1985).

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Keyhanmanesh, R., Khodamoradi, F., Rahbarghazi, R. et al. Intra-tracheal delivery of mesenchymal stem cell-conditioned medium ameliorates pathological changes by inhibiting apoptosis in asthmatic rats. Mol Biol Rep 49, 3721–3728 (2022). https://doi.org/10.1007/s11033-022-07212-8

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  • DOI: https://doi.org/10.1007/s11033-022-07212-8

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