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Mesenchymal Stromal Cells Rescue Cortical Neurons from Apoptotic Cell Death in an In Vitro Model of Cerebral Ischemia

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Abstract

Cell therapy with mesenchymal stromal cells (MSCs) was found to protect neurons from damage after experimental stroke and is currently under investigation in clinical stroke trials. In order to elucidate the mechanisms of MSC-induced neuroprotection, we used the in vitro oxygen–glucose deprivation (OGD) model of cerebral ischemia. Co-culture of primary cortical neurons with MSCs in a transwell co-culture system for 48 h prior to OGD-reduced neuronal cell death by 30–35%. Similar protection from apoptosis was observed with MSC-conditioned media when added 48 h or 30 min prior to OGD, or even after OGD. Western blot analysis revealed increased phosphorylation of STAT3 and Akt in neuronal cultures after treatment with MSC-conditioned media. Inhibition of the PI3K/Akt pathway completely abolished the neuroprotective potential of MSC-conditioned media, suggesting that MSCs can improve neuronal survival by an Akt-dependent anti-apoptotic signaling cascade. Using mass spectrometry, we identified plasminogen activator inhibitor-1 as an active compound in MSC-conditioned media. Thus, paracrine factors secreted by MSCs protect neurons from apoptotic cell death in the OGD model of cerebral ischemia.

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Acknowledgments

This study was supported by Research grant no. 01GN0508 from the German Ministry for Education and Research (BMBF). Some of the materials employed in this study were provided by the Tulane Center for Gene Therapy through a grant from NCRR of the NIH, Grant # P40RR017447. The authors thank Dr. Christel Bonnas and Dr. Dorette Freyer for their advice, and Melanie Lange, Jasmin Jamal-el-Din and Peggy Mex for excellent technical assistance.

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Authors and Affiliations

  1. Department of Neuropsychiatry and Laboratory of Molecular Psychiatry, Charité—Universitätsmedizin Berlin, Charitéplatz 1, 10117, Berlin, Germany

    Franziska Scheibe & Josef Priller

  2. Berlin-Brandenburg Center for Regenerative Therapies, Berlin, Germany

    Franziska Scheibe, Oliver Klein, Joachim Klose & Josef Priller

  3. Institute for Human Genetics, Charité—Universitätsmedizin Berlin, Augustenburger Platz 1, 13353, Berlin, Germany

    Oliver Klein & Joachim Klose

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  1. Franziska Scheibe
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Correspondence to Josef Priller.

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Scheibe, F., Klein, O., Klose, J. et al. Mesenchymal Stromal Cells Rescue Cortical Neurons from Apoptotic Cell Death in an In Vitro Model of Cerebral Ischemia. Cell Mol Neurobiol 32, 567–576 (2012). https://doi.org/10.1007/s10571-012-9798-2

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  • DOI: https://doi.org/10.1007/s10571-012-9798-2

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