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@ARTICLE{Danielyan:154066,
author = {Danielyan, Lusine and Schwab, Matthias and Siegel, Georg
and Brawek, Bianca and Garaschuk, Olga and Asavapanumas,
Nithi and Buadze, Marine and Lourhmati, Ali and Wendel,
Hans-Peter and Avci-Adali, Meltem and Krueger, Marcel A. and
Calaminus, Carsten and Naumann, Ulrike and Winter, Stefan
and Schaeffeler, Elke and Spogis, Annett and Beer-Hammer,
Sandra and Neher, Jonas J. and Spohn, Gabriele and
Kretschmer, Anja and Krämer-Albers, Eva-Maria and Barth,
Kerstin and Lee, Hong Jun and Kim, Seung U. and Frey,
William H. and Claussen, Claus D. and Hermann, Dirk M. and
Doeppner, Thorsten R. and Seifried, Erhard and Gleiter,
Christoph H. and Northoff, Hinnak and Schäfer, Richard},
title = {{C}ell motility and migration as determinants of stem cell
efficacy},
journal = {EBioMedicine},
volume = {60},
issn = {2352-3964},
address = {Amsterdam [u.a.]},
publisher = {Elsevier},
reportid = {DZNE-2021-00045},
pages = {102989},
year = {2020},
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.},
keywords = {Alzheimer Disease: therapy / Animals / Biomarkers / Cell
Movement / Cell Survival / Cell Tracking: methods / Cells,
Cultured / Disease Models, Animal / Gene Expression / Gene
Expression Profiling / Humans / Male / Membrane
Glycoproteins: genetics / Membrane Glycoproteins: metabolism
/ Mesenchymal Stem Cells: cytology / Mesenchymal Stem Cells:
physiology / Mice / Mice, Transgenic / Neural Stem Cells:
cytology / Neural Stem Cells: physiology / Oncolytic
Virotherapy / Stem Cell Transplantation / Stem Cells:
cytology / Stem Cells: physiology / Treatment Outcome},
cin = {AG Neher},
ddc = {610},
cid = {I:(DE-2719)1210012},
pnm = {342 - Disease Mechanisms and Model Systems (POF3-342)},
pid = {G:(DE-HGF)POF3-342},
typ = {PUB:(DE-HGF)16},
pmc = {pmc:PMC7494685},
pubmed = {pmid:32920368},
doi = {10.1016/j.ebiom.2020.102989},
url = {https://pub.dzne.de/record/154066},
}