EBioMedicine (Oct 2020)
Modulating endothelial adhesion and migration impacts stem cell therapies efficacy
- 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
Affiliations
- Richard Schäfer
- Institute for Transfusion Medicine and Immunohematology, German Red Cross Blood Donor Service Baden-Württemberg-Hessen gGmbH, Goethe-University Hospital, Frankfurt am Main, Germany; Institute of Clinical and Experimental Transfusion Medicine, University Hospital Tübingen, Tübingen, Germany; Corresponding author at: Institute for Transfusion Medicine and Immunohaematology, German Red Cross Blood Donor Service Baden-Württemberg-Hessen gGmbH, Sandhofstrasse 1, 60528 Frankfurt am Main, Germany.
- Matthias Schwab
- Department of Clinical Pharmacology, University Hospital Tübingen, Tübingen, Germany; Dr. Margarete Fischer-Bosch Institute of Clinical Pharmacology, Stuttgart, Germany; Department of Pharmacy and Biochemistry, University of Tübingen, Tübingen, Germany; Neuroscience Laboratory and Departments of Biochemistry and Clinical Pharmacology, Yerevan State Medical University, Yerevan, Armenia
- Georg Siegel
- Institute of Clinical and Experimental Transfusion Medicine, University Hospital Tübingen, Tübingen, Germany
- Andreas von Ameln-Mayerhofer
- Department of Pharmacy, Sindelfingen-Böblingen Medical Center, University of Tübingen, Sindelfingen, Germany
- Marine Buadze
- Department of Clinical Pharmacology, University Hospital Tübingen, Tübingen, Germany
- Ali Lourhmati
- Department of Clinical Pharmacology, University Hospital Tübingen, Tübingen, Germany
- Hans-Peter Wendel
- Departments of Thoracic, Cardiac and Vascular Surgery, University Hospital Tübingen, Tübingen, Germany
- Torsten Kluba
- Departments of Orthopaedic Surgery, University Hospital Tübingen, Tübingen, Germany
- Marcel A. Krueger
- Werner Siemens Imaging Center, Department of Preclinical Imaging and Radiopharmacy, University Hospital Tübingen, Tübingen, Germany
- Carsten Calaminus
- Werner Siemens Imaging Center, Department of Preclinical Imaging and Radiopharmacy, University Hospital Tübingen, Tübingen, Germany
- Eva Scheer
- Institute of Clinical and Experimental Transfusion Medicine, University Hospital Tübingen, Tübingen, Germany
- Massimo Dominici
- Department of Medical and Surgical Sciences for Children & Adults, University Hospital of Modena and Reggio Emilia, Modena, Italy
- Giulia Grisendi
- Department of Medical and Surgical Sciences for Children & Adults, University Hospital of Modena and Reggio Emilia, Modena, Italy
- Thorsten R. Doeppner
- Department of Neurology, University of Duisburg-Essen, Essen, Germany; Department of Neurology, University Medical Center Göttingen, Göttingen, Germany
- Jana Schlechter
- Department of Neurology, University of Duisburg-Essen, Essen, Germany
- Anne Kathrin Finzel
- Department of Clinical Pharmacology, University Hospital Tübingen, Tübingen, Germany
- Dominic Gross
- Department of Clinical Pharmacology, University Hospital Tübingen, Tübingen, Germany
- Roland Klaffschenkel
- Institute of Clinical and Experimental Transfusion Medicine, University Hospital Tübingen, Tübingen, Germany
- Frank K. Gehring
- Institute of Clinical and Experimental Transfusion Medicine, University Hospital Tübingen, Tübingen, Germany; 3T GmbH & Co. KG, Tuttlingen, Germany
- Gabriele Spohn
- Institute for Transfusion Medicine and Immunohematology, German Red Cross Blood Donor Service Baden-Württemberg-Hessen gGmbH, Goethe-University Hospital, Frankfurt am Main, Germany
- Anja Kretschmer
- Institute for Transfusion Medicine and Immunohematology, German Red Cross Blood Donor Service Baden-Württemberg-Hessen gGmbH, Goethe-University Hospital, Frankfurt am Main, Germany
- Karen Bieback
- Institute of Transfusion Medicine and Immunology, German Red Cross Blood Service Baden-Württemberg – Hessen gGmbH, Medical Faculty Mannheim, Heidelberg University, Germany
- Eva-Maria Krämer-Albers
- Institute for Developmental Biology and Neurobiology, Johannes Gutenberg University Mainz, Mainz, Germany
- Kerstin Barth
- Institute for Developmental Biology and Neurobiology, Johannes Gutenberg University Mainz, Mainz, Germany
- Anne Eckert
- Neurobiology Laboratory for Brain Aging and Mental Health, Molecular and Cognitive Neuroscience, University of Basel, Basel, Switzerland
- Stefanie Elser
- Department of Radiology, University Hospital Tübingen, Tübingen, Germany
- Joerg Schmehl
- Department of Radiology, University Hospital Tübingen, Tübingen, Germany
- Claus D. Claussen
- Department of Radiology, University Hospital Tübingen, Tübingen, Germany
- Erhard Seifried
- Institute for Transfusion Medicine and Immunohematology, German Red Cross Blood Donor Service Baden-Württemberg-Hessen gGmbH, Goethe-University Hospital, Frankfurt am Main, Germany
- Dirk M. Hermann
- Department of Neurology, University of Duisburg-Essen, Essen, Germany
- Hinnak Northoff
- Institute of Clinical and Experimental Transfusion Medicine, University Hospital Tübingen, Tübingen, Germany
- Lusine Danielyan
- Department of Clinical Pharmacology, University Hospital Tübingen, Tübingen, Germany; Department of Pharmacy and Biochemistry, University of Tübingen, Tübingen, Germany; Corresponding author at: Department of Clinical Pharmacology, University Hospital Tübingen, Auf der Morgenstelle 8, 72076 Tübingen, Germany.
- Journal volume & issue
-
Vol. 60
p. 102987
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
