Cell motility and migration as determinants of stem cell efficacy
| Autor: | Danielyan, Lusine, Schwab, Matthias, Krueger, Marcel A., Calaminus, Carsten, Naumann, Ulrike, Winter, Stefan, Schaeffeler, Elke, Spogis, Annett, Beer-Hammer, Sandra, Neher, Jonas J., Spohn, Gabriele, Kretschmer, Anja, Siegel, Georg, Krämer-Albers, Eva-Maria, Barth, Kerstin, Lee, Hong Jun, Kim, Seung U., Frey, William H., Claussen, Claus D., Hermann, Dirk M., Doeppner, Thorsten R., Seifried, Erhard, Gleiter, Christoph H., Brawek, Bianca, Northoff, Hinnak, Schäfer, Richard, Garaschuk, Olga, Asavapanumas, Nithi, Buadze, Marine, Lourhmati, Ali, Wendel, Hans-Peter, Avci-Adali, Meltem |
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| Jazyk: | angličtina |
| Rok vydání: | 2020 |
| Předmět: |
Male
Oncovirolysis methods [Cell Tracking] Cell Survival Alzheimer´s disease Medizin Gene Expression lcsh:Medicine Mice Transgenic cytology [Stem Cells] Mice cytology [Mesenchymal Stem Cells] genetics [Membrane Glycoproteins] Alzheimer Disease Cell Movement physiology [Neural Stem Cells] physiology [Stem Cells] Animals Humans physiology [Mesenchymal Stem Cells] ddc:610 cytology [Neural Stem Cells] Cells Cultured Oncolytic Virotherapy Neural stem cells lcsh:R5-920 Membrane Glycoproteins therapy [Alzheimer Disease] Gene Expression Profiling Stem Cells lcsh:R Disease Models Animal Treatment Outcome Intranasal Cell Tracking Mesenchymal stem cells Glioblastoma lcsh:Medicine (General) metabolism [Membrane Glycoproteins] Biomarkers Research Paper Stem Cell Transplantation |
| Zdroj: | EBioMedicine, Vol 60, Iss, Pp 102989-(2020) EBioMedicine EBioMedicine 60, 102989-(2020). doi:10.1016/j.ebiom.2020.102989 |
| ISSN: | 2352-3964 |
| Popis: | 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. CA extern |
| Databáze: | OpenAIRE |
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