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Paracrine Effects of Mesenchymal Stem Cells in Ischemic Stroke: Opportunities and Challenges

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Abstract

It is well acknowledged that neuroprotective effects of transplanted mesenchymal stem cells (MSCs) in ischemic stroke are attributed to their paracrine-mediated actions or bystander effects rather than to cell replacement in infarcted areas. This therapeutic plasticity is due to MSCs’ ability to secrete a broad range of bioactive molecules including growth factors, trophic factors, cytokines, chemokines, and extracellular vesicles, overall known as the secretome. The secretome derivatives, such as conditioned medium (CM) or purified extracellular vesicles (EVs), exert remarkable advantages over MSC transplantation in stroke treating. Here, in this review, we used published information to provide an overview on the secretome composition of MSCs, underlying mechanisms of therapeutic effects of MSCs, and preclinical studies on MSC-derived products application in stroke. Furthermore, we discussed current advantages and challenges for successful bench-to-bedside translation.

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Acknowledgements

This study was funded by Research Affairs (Grant No. 15695) of Shahid Beheshti University of Medical Sciences, Tehran, Iran.

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Authors and Affiliations

  1. Neuroscience Research Center, Shahid Beheshti University of Medical Sciences, Tehran, Iran

    Afsaneh Asgari Taei, Pariya Khodabakhsh & Sanaz Nasoohi

  2. Department of Neuroscience and Addiction Studies, School of Advanced Technologies in Medicine, Tehran University of Medical Sciences, Tehran, Iran

    Maryam Farahmandfar

  3. Neurobiology Research Center, Shahid Beheshti University of Medical Sciences, Tehran, Iran

    Leila Dargahi

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  1. Afsaneh Asgari Taei
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Contributions

A. Asgari Taei: performed the literature review, wrote the first draft of the manuscript, and designed the table and figures; P. Khodabakhsh: designed the table and figures; P. Khodabakhsh, S. Nasoohi, M. Farahmandfar, and L. Dargahi: overviewed the latest state of knowledge, revised and edited the manuscript; L. Dargahi: supervised the review process. All authors read and approved the final manuscript.

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Asgari Taei, A., Khodabakhsh, P., Nasoohi, S. et al. Paracrine Effects of Mesenchymal Stem Cells in Ischemic Stroke: Opportunities and Challenges. Mol Neurobiol 59, 6281–6306 (2022). https://doi.org/10.1007/s12035-022-02967-4

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