TY  - JOUR
AU  - Danielyan, Lusine
AU  - Schwab, Matthias
AU  - Siegel, Georg
AU  - Brawek, Bianca
AU  - Garaschuk, Olga
AU  - Asavapanumas, Nithi
AU  - Buadze, Marine
AU  - Lourhmati, Ali
AU  - Wendel, Hans-Peter
AU  - Avci-Adali, Meltem
AU  - Krueger, Marcel A.
AU  - Calaminus, Carsten
AU  - Naumann, Ulrike
AU  - Winter, Stefan
AU  - Schaeffeler, Elke
AU  - Spogis, Annett
AU  - Beer-Hammer, Sandra
AU  - Neher, Jonas J.
AU  - Spohn, Gabriele
AU  - Kretschmer, Anja
AU  - Krämer-Albers, Eva-Maria
AU  - Barth, Kerstin
AU  - Lee, Hong Jun
AU  - Kim, Seung U.
AU  - Frey, William H.
AU  - Claussen, Claus D.
AU  - Hermann, Dirk M.
AU  - Doeppner, Thorsten R.
AU  - Seifried, Erhard
AU  - Gleiter, Christoph H.
AU  - Northoff, Hinnak
AU  - Schäfer, Richard
TI  - Cell motility and migration as determinants of stem cell efficacy
JO  - EBioMedicine
VL  - 60
SN  - 2352-3964
CY  - Amsterdam [u.a.]
PB  - Elsevier
M1  - DZNE-2021-00045
SP  - 102989
PY  - 2020
AB  - 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.
KW  - Alzheimer Disease: therapy
KW  - Animals
KW  - Biomarkers
KW  - Cell Movement
KW  - Cell Survival
KW  - Cell Tracking: methods
KW  - Cells, Cultured
KW  - Disease Models, Animal
KW  - Gene Expression
KW  - Gene Expression Profiling
KW  - Humans
KW  - Male
KW  - Membrane Glycoproteins: genetics
KW  - Membrane Glycoproteins: metabolism
KW  - Mesenchymal Stem Cells: cytology
KW  - Mesenchymal Stem Cells: physiology
KW  - Mice
KW  - Mice, Transgenic
KW  - Neural Stem Cells: cytology
KW  - Neural Stem Cells: physiology
KW  - Oncolytic Virotherapy
KW  - Stem Cell Transplantation
KW  - Stem Cells: cytology
KW  - Stem Cells: physiology
KW  - Treatment Outcome
LB  - PUB:(DE-HGF)16
C2  - pmc:PMC7494685
C6  - pmid:32920368
DO  - DOI:10.1016/j.ebiom.2020.102989
UR  - https://pub.dzne.de/record/154066
ER  -