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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},
}