TY  - JOUR
AU  - Blaschke, Stefan
AU  - Vay, Sabine Ulrike
AU  - Pallast, Niklas
AU  - Rabenstein, Monika
AU  - Abraham, Jella-Andrea
AU  - Linnartz, Christina
AU  - Hoffmann, Marco
AU  - Hersch, Nils
AU  - Merkel, Rudolf
AU  - Hoffmann, Bernd
AU  - Fink, Gereon Rudolf
AU  - Rueger, Maria Adele
TI  - Substrate elasticity induces quiescence and promotes neurogenesis of primary neural stem cells - a biophysical in vitro model of the physiological cerebral milieu
JO  - Journal of tissue engineering and regenerative medicine
VL  - 13
IS  - 6
SN  - 1932-6254
CY  - Hoboken, NJ [u.a.]
PB  - Wiley
M1  - FZJ-2019-01735
SP  - 960-972
PY  - 2019
AB  - 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.
LB  - PUB:(DE-HGF)16
C6  - pmid:30815982
UR  - <Go to ISI:>//WOS:000473660800005
DO  - DOI:10.1002/term.2838
UR  - https://juser.fz-juelich.de/record/861214
ER  -