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The Efficacy of Stem Cells Secretome Application in Osteoarthritis: A Systematic Review of In Vivo Studies

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Abstract

Purpose

Mesenchymal stem cells (MSCs) have appeared as a promising regenerative cell-based therapeutic, for degenerative conditions, such as OA, while the beneficial results from the application of MSCs have been attributed to the MSCs-derived secretome, which is the sum of cytoprotective factors produced by the MSCs. Aim of this study was to systematically review the literature in order to assess whether stem cell secretome (conditioned medium-CM, exosome-Exos or microvesicles-MV)(CM/Exos/MVs) treatment reduces inflammation and enhances cartilage regeneration in preclinical studies of experimental arthritis.

Materials and Methods

An extensive electronic search was conducted by 2 independent reviewers by using the PubMed, Cochrane Library, Web of Science, and Scopus database, as well as Google Scholar, in order to identify the studies that met our inclusion criteria until August 2019. Included studies were assessed for quality and Risk of Bias (RoB) using the ARRIVE (Animal Research: Reporting In Vivo Experiments) guidelines and a modification of Systematic Review Centre for Laboratory animal Experimentation (SYRCLE) RoB tool for animal studies, respectively.

Results

The initial search provided 525 records, with 28 fulfilling the inclusion criteria. The included studies presented great heterogeneity regarding the stem cells used, the preparation of therapeutic agent as well as the animal models used for testing. In addition, most studies presented with an unclear or high risk bias.

Conclusion

In summary, the positive results of CM/Exos/MVs application in preclinical models of experimentally induced OA in terms of resolution of inflammation and cartilage regeneration are highlighted in this review, presenting a promising therapeutic solution for OA.

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Acknowledgments

This study was supported by a scholarship from the Greek State Scholarship Foundation (IKY), funded by the action “Enhancing human research potential through doctoral research” from resources of the European Program “Development of Human Potential, Education and Lifelong Learning”, 2014-2020 funded by the European Social Fund (ESF) and National Resources.

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Authors and Affiliations

  1. Department of Prosthodontics, Faculty of Dentistry, Aristotle University of Thessaloniki, University Campus, Dentistry Building, GR-54124, Thessaloniki, Greece

    Maria Bousnaki, Athina Bakopoulou & Petros Koidis

  2. Department of Physiology and Pharmacology, Faculty of Medicine, Aristotle University of Thessaloniki, University Campus, GR-54006, Thessaloniki, Greece

    Aristeidis Kritis

  3. cGMP Regenerative Medicine facility, Department of Physiology and Pharmacology, School of Medicine, Aristotle University of Thessaloniki (A.U.TH.), Thessaloniki, Greece

    Aristeidis Kritis

Authors
  1. Maria Bousnaki
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  2. Athina Bakopoulou
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  3. Aristeidis Kritis
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  4. Petros Koidis
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Contributions

MB: conceive the study, systematic search, screening for eligibility, data extraction, bias and quality assessment, and drafting of the manuscript. AB: systematic search, screening for eligibility and drafting the manuscript. AK: drafting the manuscript. PK: bias and quality assessment, and drafting the manuscript. All authors: interpretation of data, critical revision for important intellectual content, approval of the final version of the manuscript to be published, and agreement to be accountable for all aspects of the work in ensuring that questions related to the accuracy or integrity of any part of the work are appropriately investigated and resolved.

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Correspondence to Maria Bousnaki.

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Bousnaki, M., Bakopoulou, A., Kritis, A. et al. The Efficacy of Stem Cells Secretome Application in Osteoarthritis: A Systematic Review of In Vivo Studies. Stem Cell Rev and Rep 16, 1222–1241 (2020). https://doi.org/10.1007/s12015-020-09980-x

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  • DOI: https://doi.org/10.1007/s12015-020-09980-x

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