EBioMedicine (Oct 2020)
Cell motility and migration as determinants of stem cell efficacy
- Lusine Danielyan,
- Matthias Schwab,
- Georg Siegel,
- Bianca Brawek,
- Olga Garaschuk,
- Nithi Asavapanumas,
- Marine Buadze,
- Ali Lourhmati,
- Hans-Peter Wendel,
- Meltem Avci-Adali,
- Marcel A. Krueger,
- Carsten Calaminus,
- Ulrike Naumann,
- Stefan Winter,
- Elke Schaeffeler,
- Annett Spogis,
- Sandra Beer-Hammer,
- Jonas J. Neher,
- Gabriele Spohn,
- Anja Kretschmer,
- Eva-Maria Krämer-Albers,
- Kerstin Barth,
- Hong Jun Lee,
- Seung U. Kim,
- William H. Frey, II,
- Claus D. Claussen,
- Dirk M. Hermann,
- Thorsten R. Doeppner,
- Erhard Seifried,
- Christoph H. Gleiter,
- Hinnak Northoff,
- Richard Schäfer
Affiliations
- Lusine Danielyan
- Department of Clinical Pharmacology, University Hospital Tübingen, Tübingen, Germany; Neuroscience Laboratory and Departments of Biochemistry and Clinical Pharmacology, Yerevan State Medical University, Yerevan, Armenia; Corresponding author at: Department of Clinical Pharmacology, University Hospital Tübingen, Auf der Morgenstelle 8, 72076 Tübingen, Germany.
- Matthias Schwab
- Department of Clinical Pharmacology, University Hospital Tübingen, Tübingen, Germany; Neuroscience Laboratory and Departments of Biochemistry and Clinical Pharmacology, Yerevan State Medical University, Yerevan, Armenia; Dr. Margarete Fischer-Bosch Institute of Clinical Pharmacology, Stuttgart, Germany and University of Tübingen, Tübingen, Germany; Department of Pharmacy and Biochemistry, University of Tübingen, Tübingen, Germany
- Georg Siegel
- Institute of Clinical and Experimental Transfusion Medicine, University Hospital Tübingen, Tübingen, Germany
- Bianca Brawek
- Institute of Physiology, Department of Neurophysiology, University of Tübingen, Tübingen, Germany
- Olga Garaschuk
- Institute of Physiology, Department of Neurophysiology, University of Tübingen, Tübingen, Germany
- Nithi Asavapanumas
- Institute of Physiology, Department of Neurophysiology, University of Tübingen, Tübingen, 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
- Department of Thoracic, Cardiac and Vascular Surgery, University Hospital Tübingen, Tübingen, Germany
- Meltem Avci-Adali
- Department of Thoracic, Cardiac and Vascular 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
- Ulrike Naumann
- Hertie Institute for Clinical Brain Research and Center Neurology, Department of Vascular Neurology, Tübingen Neuro-Campus (TNC), University of Tübingen, Tübingen, Germany
- Stefan Winter
- Dr. Margarete Fischer-Bosch Institute of Clinical Pharmacology, Stuttgart, Germany and University of Tübingen, Tübingen, Germany
- Elke Schaeffeler
- Dr. Margarete Fischer-Bosch Institute of Clinical Pharmacology, Stuttgart, Germany and University of Tübingen, Tübingen, Germany
- Annett Spogis
- Department of Clinical Pharmacology, University Hospital Tübingen, Tübingen, Germany
- Sandra Beer-Hammer
- Department of Pharmacology, Experimental Therapy and Toxicology, Institute of Experimental and Clinical Pharmacology and Pharmacogenomic, and ICePhA, University Hospital Tübingen, Tübingen, Germany
- Jonas J. Neher
- Department of Cellular Neurology, Hertie Institute for Clinical Brain Research, University of Tübingen, Tübingen, Germany; German Center for Neurodegenerative Diseases (DZNE), Tübingen, Tübingen, 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
- 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
- Hong Jun Lee
- College of Medicine and Medical Research Institute, Chungbuk National University, Cheongju, Chungbuk, Republic of Korea; Research Institute eBiogen Inc., Seoul, Republic of Korea
- Seung U. Kim
- Division of Neurology, Department of Medicine, UBC Hospital, University of British Columbia, Vancouver, BC, Canada
- William H. Frey, II
- HealthPartners Center for Memory and Aging, HealthPartners Neurosciences, St. Paul, MN, U.S.A.
- Claus D. Claussen
- Department of Radiology, University Hospital Tübingen, Tübingen, Germany
- Dirk M. Hermann
- Department of Neurology, University of Duisburg-Essen, Essen, Germany
- Thorsten R. Doeppner
- Department of Neurology, University of Duisburg-Essen, Essen, Germany; Department of Neurology, University Medical Center Göttingen, Göttingen, 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
- Christoph H. Gleiter
- Department of Clinical Pharmacology, University Hospital Tübingen, Tübingen, Germany
- Hinnak Northoff
- Institute of Clinical and Experimental Transfusion Medicine, University Hospital Tübingen, Tübingen, Germany
- Richard Schäfer
- Institute of Clinical and Experimental Transfusion Medicine, University Hospital Tübingen, Tübingen, Germany; Institute for Transfusion Medicine and Immunohematology, German Red Cross Blood Donor Service Baden-Württemberg-Hessen gGmbH, Goethe-University Hospital, Frankfurt am Main, 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.
- Journal volume & issue
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Vol. 60
p. 102989
Abstract
Background: Stem cells` (SC) functional heterogeneity and its poorly understood aetiology impedes clinical development of cell-based therapies in regenerative medicine and oncology. Recent studies suggest a strong correlation between the SC migration potential and their therapeutic efficacy in humans. Designating SC migration as a denominator of functional SC heterogeneity, we sought to identify highly migrating subpopulations within different SC classes and evaluate their therapeutic properties in comparison to the parental non-selected cells. Methods: We selected highly migrating subpopulations from mesenchymal and neural SC (sMSC and sNSC), characterized their features including but not limited to migratory potential, trophic factor release and transcriptomic signature. To assess lesion-targeted migration and therapeutic properties of isolated subpopulations in vivo, surgical transplantation and intranasal administration of MSCs in mouse models of glioblastoma and Alzheimer's disease respectively were performed. Findings: Comparison of parental non-selected cells with isolated subpopulations revealed superior motility and migratory potential of sMSC and sNSC in vitro. We identified podoplanin as a major regulator of migratory features of sMSC/sNSC. Podoplanin engineering improved oncovirolytic activity of virus-loaded NSC on distantly located glioblastoma cells. Finally, sMSC displayed more targeted migration to the tumour site in a mouse glioblastoma model and remarkably higher potency to reduce pathological hallmarks and memory deficits in transgenic Alzheimer's disease mice. Interpretation: Functional heterogeneity of SC is associated with their motility and migration potential which can serve as predictors of SC therapeutic efficacy. Funding: This work was supported in part by the Robert Bosch Stiftung (Stuttgart, Germany) and by the IZEPHA grant.
