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@ARTICLE{Blaschke:861214,
      author       = {Blaschke, Stefan and Vay, Sabine Ulrike and Pallast, Niklas
                      and Rabenstein, Monika and Abraham, Jella-Andrea and
                      Linnartz, Christina and Hoffmann, Marco and Hersch, Nils and
                      Merkel, Rudolf and Hoffmann, Bernd and Fink, Gereon Rudolf
                      and Rueger, Maria Adele},
      title        = {{S}ubstrate elasticity induces quiescence and promotes
                      neurogenesis of primary neural stem cells - a biophysical in
                      vitro model of the physiological cerebral milieu},
      journal      = {Journal of tissue engineering and regenerative medicine},
      volume       = {13},
      number       = {6},
      issn         = {1932-6254},
      address      = {Hoboken, NJ [u.a.]},
      publisher    = {Wiley},
      reportid     = {FZJ-2019-01735},
      pages        = {960-972},
      year         = {2019},
      abstract     = {In the brain, neural stem cells (NSC) are tightly regulated
                      by external signals and biophysical cues mediated by the
                      local microenvironment or “niche.” In particular, the
                      influence of tissue elasticity, known to fundamentally
                      affect the function of various cell types in the body, on
                      NSC remains poorly understood. We, accordingly, aimed to
                      characterize the effects of elastic substrates on critical
                      NSC functions. Primary rat NSC were grown as monolayers on
                      polydimethylsiloxane‐ (PDMS‐) based gels. PDMS‐coated
                      cell culture plates, simulating the physiological
                      microenvironment of the living brain, were generated in
                      various degrees of elasticity, ranging from 1 to 50 kPa;
                      additionally, results were compared with regular glass
                      plates as usually used in cell culture work. Survival of NSC
                      on the PDMS‐based substrates was unimpaired. The
                      proliferation rate on 1 kPa PDMS decreased by $45\%$
                      compared with stiffer PMDS substrates of 50 kPa (p < 0.05)
                      whereas expression of cyclin‐dependent kinase inhibitor
                      1B/p27Kip1 increased more than two fold (p < 0.01),
                      suggesting NSC quiescence. NSC differentiation was
                      accelerated on softer substrates and favored the generation
                      of neurons $(42\%$ neurons on 1 kPa PDMS vs. $25\%$ on 50
                      kPa PDMS; p < 0.05). Neurons generated on 1 kPa PDMS showed
                      $29\%$ longer neurites compared with those on stiffer PDMS
                      substrates (p < 0.05), suggesting optimized neuronal
                      maturation and an accelerated generation of neuronal
                      networks. Data show that primary NSC are significantly
                      affected by the mechanical properties of their
                      microenvironment. Culturing NSC on a substrate of
                      brain‐like elasticity keeps them in their physiological,
                      quiescent state and increases their neurogenic potential.},
      cin          = {INM-3 / ICS-7},
      ddc          = {610},
      cid          = {I:(DE-Juel1)INM-3-20090406 / I:(DE-Juel1)ICS-7-20110106},
      pnm          = {572 - (Dys-)function and Plasticity (POF3-572)},
      pid          = {G:(DE-HGF)POF3-572},
      typ          = {PUB:(DE-HGF)16},
      pubmed       = {pmid:30815982},
      UT           = {WOS:000473660800005},
      doi          = {10.1002/term.2838},
      url          = {https://juser.fz-juelich.de/record/861214},
}