Modulating endothelial adhesion and migration impacts stem cell therapies efficacy

EBioMedicine

Claus D. Claussen¹  Roland Klaffschenkel²  Gabriele Spohn²  Erhard Seifried³  Georg Siegel⁴  Karen Bieback⁵  Ali Lourhmati⁶  Marine Buadze⁷  Matthias Schwab⁸  Hans-Peter Wendel⁹  Carsten Calaminus^1,10  Anne Eckert^1,10  Eva Scheer^1,10  Kerstin Barth^1,10  Andreas von Ameln-Mayerhofer^1,10  Frank K. Gehring^1,11  Dominic Gross^1,11  Anja Kretschmer^1,12  Eva-Maria Krämer-Albers^1,12  Marcel A. Krueger^1,13  Giulia Grisendi^1,14  Massimo Dominici^1,15  Anne Kathrin Finzel^1,16  Torsten Kluba^1,16  Stefanie Elser^1,16  Joerg Schmehl^1,16  Lusine Danielyan^1,17  Dirk M. Hermann^1,18  Richard Schäfer^1,18  Hinnak Northoff^1,18  Jana Schlechter^1,19  Thorsten R. Doeppner^1,19 

[1] 3T GmbH &Adults, University Hospital of Modena and Reggio Emilia, Modena, Italy;Co. KG, Tuttlingen, 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.;Department of Neurology, University Medical Center Göttingen, Göttingen, Germany;Department of Pharmacy and Biochemistry, University of Tübingen, Tübingen, Germany;Dr. Margarete Fischer-Bosch Institute of Clinical Pharmacology, Stuttgart, Germany;Institute of Clinical and Experimental Transfusion Medicine, University Hospital Tübingen, Tübingen, Germany;Neuroscience Laboratory and Departments of Biochemistry and Clinical Pharmacology, Yerevan State Medical University, Yerevan, Armenia;Department of Clinical Pharmacology, University Hospital Tübingen, Tübingen, Germany;;Department of Medical and Surgical Sciences for Children &Department of Neurology, University of Duisburg-Essen, Essen, Germany;Department of Pharmacy, Sindelfingen-Böblingen Medical Center, University of Tübingen, Sindelfingen, Germany;Departments of Orthopaedic Surgery, University Hospital Tübingen, Tübingen, Germany;Departments of Thoracic, Cardiac and Vascular Surgery, University Hospital Tübingen, Tübingen, Germany;Institute of Clinical and Experimental Transfusion Medicine, University Hospital Tübingen, Tübingen, Germany;Institute of Transfusion Medicine and Immunology, German Red Cross Blood Service Baden-Württemberg – Hessen gGmbH, Medical Faculty Mannheim, Heidelberg University, Germany;Institute for Transfusion Medicine and Immunohematology, German Red Cross Blood Donor Service Baden-Württemberg-Hessen gGmbH, Goethe-University Hospital, Frankfurt am Main, Germany;Werner Siemens Imaging Center, Department of Preclinical Imaging and Radiopharmacy, University Hospital Tübingen, Tübingen, Germany;

关键词: Stem cells;    Migration;    Adhesion;    Homing;    Stroke;    Glioma;   

DOI  :  

来源: DOAJ

【 摘 要 】

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

【 授权许可】

Unknown