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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 w...
Autores principales: | , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Elsevier
2020
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7498853/ https://www.ncbi.nlm.nih.gov/pubmed/32942121 http://dx.doi.org/10.1016/j.ebiom.2020.102987 |
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author | Schäfer, Richard Schwab, Matthias Siegel, Georg von Ameln-Mayerhofer, Andreas Buadze, Marine Lourhmati, Ali Wendel, Hans-Peter Kluba, Torsten Krueger, Marcel A. Calaminus, Carsten Scheer, Eva Dominici, Massimo Grisendi, Giulia Doeppner, Thorsten R. Schlechter, Jana Finzel, Anne Kathrin Gross, Dominic Klaffschenkel, Roland Gehring, Frank K. Spohn, Gabriele Kretschmer, Anja Bieback, Karen Krämer-Albers, Eva-Maria Barth, Kerstin Eckert, Anne Elser, Stefanie Schmehl, Joerg Claussen, Claus D. Seifried, Erhard Hermann, Dirk M. Northoff, Hinnak Danielyan, Lusine |
author_facet | Schäfer, Richard Schwab, Matthias Siegel, Georg von Ameln-Mayerhofer, Andreas Buadze, Marine Lourhmati, Ali Wendel, Hans-Peter Kluba, Torsten Krueger, Marcel A. Calaminus, Carsten Scheer, Eva Dominici, Massimo Grisendi, Giulia Doeppner, Thorsten R. Schlechter, Jana Finzel, Anne Kathrin Gross, Dominic Klaffschenkel, Roland Gehring, Frank K. Spohn, Gabriele Kretschmer, Anja Bieback, Karen Krämer-Albers, Eva-Maria Barth, Kerstin Eckert, Anne Elser, Stefanie Schmehl, Joerg Claussen, Claus D. Seifried, Erhard Hermann, Dirk M. Northoff, Hinnak Danielyan, Lusine |
author_sort | Schäfer, Richard |
collection | PubMed |
description | 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 |
format | Online Article Text |
id | pubmed-7498853 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2020 |
publisher | Elsevier |
record_format | MEDLINE/PubMed |
spelling | pubmed-74988532020-09-25 Modulating endothelial adhesion and migration impacts stem cell therapies efficacy Schäfer, Richard Schwab, Matthias Siegel, Georg von Ameln-Mayerhofer, Andreas Buadze, Marine Lourhmati, Ali Wendel, Hans-Peter Kluba, Torsten Krueger, Marcel A. Calaminus, Carsten Scheer, Eva Dominici, Massimo Grisendi, Giulia Doeppner, Thorsten R. Schlechter, Jana Finzel, Anne Kathrin Gross, Dominic Klaffschenkel, Roland Gehring, Frank K. Spohn, Gabriele Kretschmer, Anja Bieback, Karen Krämer-Albers, Eva-Maria Barth, Kerstin Eckert, Anne Elser, Stefanie Schmehl, Joerg Claussen, Claus D. Seifried, Erhard Hermann, Dirk M. Northoff, Hinnak Danielyan, Lusine EBioMedicine Research Paper 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 Elsevier 2020-09-14 /pmc/articles/PMC7498853/ /pubmed/32942121 http://dx.doi.org/10.1016/j.ebiom.2020.102987 Text en © 2020 The Authors http://creativecommons.org/licenses/by-nc-nd/4.0/ This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/). |
spellingShingle | Research Paper Schäfer, Richard Schwab, Matthias Siegel, Georg von Ameln-Mayerhofer, Andreas Buadze, Marine Lourhmati, Ali Wendel, Hans-Peter Kluba, Torsten Krueger, Marcel A. Calaminus, Carsten Scheer, Eva Dominici, Massimo Grisendi, Giulia Doeppner, Thorsten R. Schlechter, Jana Finzel, Anne Kathrin Gross, Dominic Klaffschenkel, Roland Gehring, Frank K. Spohn, Gabriele Kretschmer, Anja Bieback, Karen Krämer-Albers, Eva-Maria Barth, Kerstin Eckert, Anne Elser, Stefanie Schmehl, Joerg Claussen, Claus D. Seifried, Erhard Hermann, Dirk M. Northoff, Hinnak Danielyan, Lusine Modulating endothelial adhesion and migration impacts stem cell therapies efficacy |
title | Modulating endothelial adhesion and migration impacts stem cell therapies efficacy |
title_full | Modulating endothelial adhesion and migration impacts stem cell therapies efficacy |
title_fullStr | Modulating endothelial adhesion and migration impacts stem cell therapies efficacy |
title_full_unstemmed | Modulating endothelial adhesion and migration impacts stem cell therapies efficacy |
title_short | Modulating endothelial adhesion and migration impacts stem cell therapies efficacy |
title_sort | modulating endothelial adhesion and migration impacts stem cell therapies efficacy |
topic | Research Paper |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7498853/ https://www.ncbi.nlm.nih.gov/pubmed/32942121 http://dx.doi.org/10.1016/j.ebiom.2020.102987 |
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