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Modulating endothelial adhesion and migration impacts stem cell therapies efficacy

Background - Limited knowledge of stem cell therapies` mechanisms of action hampers their sustainable implementation into the clinic. Specifically, the interactions of transplanted stem cells with the host vasculature and its implications for their therapeutic efficacy are not elucidated. We tested...

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Main Authors: Schäfer, Richard (Author) , Schwab, Matthias (Author) , Siegel, Georg (Author) , Ameln-Mayerhofer, Andreas von (Author) , Buadze, Marine (Author) , Lourhmati, Ali (Author) , Wendel, Hans-Peter (Author) , Kluba, Torsten (Author) , Krueger, Marcel A. (Author) , Calaminus, Carsten (Author) , Scheer, Eva (Author) , Dominici, Massimo (Author) , Grisendi, Giulia (Author) , Doeppner, Thorsten R. (Author) , Schlechter, Jana (Author) , Finzel, Anne Kathrin (Author) , Gross, Dominic (Author) , Klaffschenkel, Roland (Author) , Gehring, Frank K. (Author) , Spohn, Gabriele (Author) , Kretschmer, Anja (Author) , Bieback, Karen (Author) , Krämer-Albers, Eva-Maria (Author) , Barth, Kerstin (Author) , Eckert, Anne (Author) , Elser, Stefanie (Author) , Schmehl, Joerg (Author) , Claussen, Claus D. (Author) , Seifried, Erhard (Author) , Hermann, Dirk M. (Author) , Northoff, Hinnak (Author) , Danielyan, Lusine (Author)
Format: Article (Journal)
Language:English
Published: October 2020
In: EBioMedicine
Year: 2020, Volume: 60, Pages: 1-15
ISSN:2352-3964
DOI:10.1016/j.ebiom.2020.102987
Online Access:Verlag, lizenzpflichtig, Volltext: https://doi.org/10.1016/j.ebiom.2020.102987
Verlag, lizenzpflichtig, Volltext: https://www.sciencedirect.com/science/article/pii/S2352396420303637
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Author Notes:Richard Schäfer, Matthias Schwab, Georg Siegel, Andreas von Ameln-Mayerhofer, Marine Buadze, Ali Lourhmati, Hans-Peter Wendel, Torsten Kluba, Marcel A. Krueger, Carsten Calaminus, Eva Scheer, Massimo Dominici, Giulia Grisendi, Thorsten R. Doeppner, Jana Schlechter, Anne Kathrin Finzel, Dominic Gross, Roland Klaffschenkel, Frank K. Gehring, Gabriele Spohn, Anja Kretschmer, Karen Bieback, Eva-Maria Krämer-Albers, Kerstin Barth, Anne Eckert, Stefanie Elser, Joerg Schmehl, Claus D. Claussen, Erhard Seifried, Dirk M. Hermann, Hinnak Northoff, Lusine Danielyan
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Summary:Background - Limited knowledge of stem cell therapies` mechanisms of action hampers their sustainable implementation into the clinic. Specifically, the interactions of transplanted stem cells with the host vasculature and its implications for their therapeutic efficacy are not elucidated. We tested whether adhesion receptors and chemokine receptors on stem cells can be functionally modulated, and consequently if such modulation may substantially affect therapeutically relevant stem cell interactions with the host endothelium. - Methods - We investigated the effects of cationic molecule polyethylenimine (PEI) treatment with or without nanoparticles on the functions of adhesion receptors and chemokine receptors of human bone marrow-derived Mesenchymal Stem Cells (MSC). Analyses included MSC functions in vitro, as well as homing and therapeutic efficacy in rodent models of central nervous system´s pathologies in vivo. - Findings - PEI treatment did not affect viability, immunomodulation or differentiation potential of MSC, but increased the CCR4 expression and functionally blocked their adhesion receptors, thus decreasing their adhesion capacity in vitro. Intravenously applied in a rat model of brain injury, the homing rate of PEI-MSC in the brain was highly increased with decreased numbers of adherent PEI-MSC in the lung vasculature. Moreover, in comparison to untreated MSC, PEI-MSC featured increased tumour directed migration in a mouse glioblastoma model, and superior therapeutic efficacy in a murine model of stroke. - Interpretation - Balanced stem cell adhesion and migration in different parts of the vasculature and tissues together with the local microenvironment impacts their therapeutic efficacy. - Funding - Robert Bosch Stiftung, IZEPHA grant, EU grant 7 FP Health
Item Description:Gesehen am 24.07.2025
Physical Description:Online Resource
ISSN:2352-3964
DOI:10.1016/j.ebiom.2020.102987

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