Journal Article

DZNE-2021-00045

http://join2-wiki.gsi.de/foswiki/pub/Main/Artwork/join2_logo100x88.png Cell motility and migration as determinants of stem cell efficacy

Danielyan, L. (Corresponding author) ; Schwab, M. ; Siegel, G. ; Brawek, B. ; Garaschuk, O. ; Asavapanumas, N. ; Buadze, M. ; Lourhmati, A. ; Wendel, H.-P. ; Avci-Adali, M. ; Krueger, M. A. ; Calaminus, C. ; Naumann, U. ; Winter, S. ; Schaeffeler, E. ; Spogis, A. ; Beer-Hammer, S. ; Neher, J. J.DZNE* ; Spohn, G. ; Kretschmer, A. ; Krämer-Albers, E.-M. ; Barth, K. ; Lee, H. J. ; Kim, S. U. ; Frey, W. H. ; Claussen, C. D. ; Hermann, D. M. ; Doeppner, T. R. ; Seifried, E. ; Gleiter, C. H. ; Northoff, H. ; Schäfer, R. (Corresponding author)

2020
Elsevier Amsterdam [u.a.]

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Please use a persistent id in citations: doi:10.1016/j.ebiom.2020.102989

Abstract: BackgroundStem 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.MethodsWe 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.FindingsComparison 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.InterpretationFunctional heterogeneity of SC is associated with their motility and migration potential which can serve as predictors of SC therapeutic efficacy.FundingThis work was supported in part by the Robert Bosch Stiftung (Stuttgart, Germany) and by the IZEPHA grant.

Keyword(s): Alzheimer Disease: therapy (MeSH) ; Animals (MeSH) ; Biomarkers (MeSH) ; Cell Movement (MeSH) ; Cell Survival (MeSH) ; Cell Tracking: methods (MeSH) ; Cells, Cultured (MeSH) ; Disease Models, Animal (MeSH) ; Gene Expression (MeSH) ; Gene Expression Profiling (MeSH) ; Humans (MeSH) ; Male (MeSH) ; Membrane Glycoproteins: genetics (MeSH) ; Membrane Glycoproteins: metabolism (MeSH) ; Mesenchymal Stem Cells: cytology (MeSH) ; Mesenchymal Stem Cells: physiology (MeSH) ; Mice (MeSH) ; Mice, Transgenic (MeSH) ; Neural Stem Cells: cytology (MeSH) ; Neural Stem Cells: physiology (MeSH) ; Oncolytic Virotherapy (MeSH) ; Stem Cell Transplantation (MeSH) ; Stem Cells: cytology (MeSH) ; Stem Cells: physiology (MeSH) ; Treatment Outcome (MeSH)

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Contributing Institute(s):

1. Neuroimmunology and Neurodegenerative Disease (AG Neher)

Research Program(s):

1. 342 - Disease Mechanisms and Model Systems (POF3-342) (POF3-342)

Appears in the scientific report 2020

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Database coverage:
; ; ; ; Article Processing Charges ; Clarivate Analytics Master Journal List ; DOAJ Seal ; Essential Science Indicators ; Fees ; IF >= 10 ; JCR ; SCOPUS ; Science Citation Index Expanded ; Web of Science Core Collection

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