Universität zu Köln

Blaschke, Stefan, Vay, Sabine Ulrike, Pallast, Niklas, Rabenstein, Monika, Abraham, Jella-Andrea, Linnartz, Christina, Hoffmann, Marco, Hersch, Nils, Merkel, Rudolf ORCID: 0000-0003-3178-3282, Hoffmann, Bernd ORCID: 0000-0002-3803-8835, Fink, Gereon Rudolf and Rueger, Maria Adele (2019). Substrate elasticity induces quiescence and promotes neurogenesis of primary neural stem cells-A biophysical in vitro model of the physiological cerebral milieu. J. Tissue Eng. Regen. Med., 13 (6). S. 960 - 973. HOBOKEN: WILEY. ISSN 1932-7005

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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.

Item Type:	Journal Article
Creators:	Creators Email ORCID ORCID Put Code Blaschke, Stefan UNSPECIFIED UNSPECIFIED UNSPECIFIED Vay, Sabine Ulrike UNSPECIFIED UNSPECIFIED UNSPECIFIED Pallast, Niklas UNSPECIFIED UNSPECIFIED UNSPECIFIED Rabenstein, Monika UNSPECIFIED UNSPECIFIED UNSPECIFIED Abraham, Jella-Andrea UNSPECIFIED UNSPECIFIED UNSPECIFIED Linnartz, Christina UNSPECIFIED UNSPECIFIED UNSPECIFIED Hoffmann, Marco UNSPECIFIED UNSPECIFIED UNSPECIFIED Hersch, Nils UNSPECIFIED UNSPECIFIED UNSPECIFIED Merkel, Rudolf UNSPECIFIED orcid.org/0000-0003-3178-3282 UNSPECIFIED Hoffmann, Bernd UNSPECIFIED orcid.org/0000-0002-3803-8835 UNSPECIFIED Fink, Gereon Rudolf UNSPECIFIED UNSPECIFIED UNSPECIFIED Rueger, Maria Adele UNSPECIFIED UNSPECIFIED UNSPECIFIED
URN:	urn:nbn:de:hbz:38-146061
DOI:	10.1002/term.2838
Journal or Publication Title:	J. Tissue Eng. Regen. Med.
Volume:	13
Number:	6
Page Range:	S. 960 - 973
Date:	2019
Publisher:	WILEY
Place of Publication:	HOBOKEN
ISSN:	1932-7005
Language:	English
Faculty:	Unspecified
Divisions:	Unspecified
Subjects:	no entry
Uncontrolled Keywords:	Keywords Language VISCOELASTIC PROPERTIES; HEMATOPOIETIC STEM; MATRIX ELASTICITY; MR ELASTOGRAPHY; TISSUE; BRAIN; DIFFERENTIATION; STIFFNESS; SOFT; MECHANOTRANSDUCTION Multiple languages Cell & Tissue Engineering; Biotechnology & Applied Microbiology; Cell Biology; Engineering, Biomedical Multiple languages
Refereed:	Yes
URI:	http://kups.ub.uni-koeln.de/id/eprint/14606