1. Modulating endothelial adhesion and migration impacts stem cell therapies efficacy.
- Author
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Schäfer R, Schwab M, Siegel G, von Ameln-Mayerhofer A, Buadze M, Lourhmati A, Wendel HP, Kluba T, Krueger MA, Calaminus C, Scheer E, Dominici M, Grisendi G, Doeppner TR, Schlechter J, Finzel AK, Gross D, Klaffschenkel R, Gehring FK, Spohn G, Kretschmer A, Bieback K, Krämer-Albers EM, Barth K, Eckert A, Elser S, Schmehl J, Claussen CD, Seifried E, Hermann DM, Northoff H, and Danielyan L
- Subjects
- Animals, Biomarkers, Cell Differentiation, Cell Line, Cell- and Tissue-Based Therapy, Cells, Cultured, Cellular Microenvironment, Disease Models, Animal, Glioma diagnosis, Glioma pathology, Glioma therapy, Humans, Immunophenotyping, Mesenchymal Stem Cell Transplantation, Mesenchymal Stem Cells metabolism, Mice, Rats, Stem Cell Transplantation, Xenograft Model Antitumor Assays, Cell Adhesion, Cell Movement, Endothelium metabolism, Stem Cells metabolism
- Abstract
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., Competing Interests: Declaration of Competing Interest Dr. Danielyan reports grants from IZEPHA, during the conduct of the study. Dr. Schwab reports grants from Robert Bosch Stiftung (Stuttgart, Germany) during the conduct of the study. Dr. Schäfer reports a grant from the Commission of the European Communities during the conduct of the study. Dres Schäfer, Danielyan, von Ameln-Mayerhofer, Wendel, Kluba, Dominici, Claussen, Northoff and Siegel have a patent DE102012111891.4.; EP13801557.3. Dr. Gehring is a shareholder of 3T analytic. All other authors have no competing interests., (Copyright © 2020 The Authors. Published by Elsevier B.V. All rights reserved.)
- Published
- 2020
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