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Differentiation of a Human Neural Stem Cell Line on Three Dimensional Cultures, Analysis of MicroRNA and Putative Target Genes
Published on: April 12, 2015
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Surface topography during neural stem cell differentiation regulates cell migration and cell morphology
Catherine Czeisler1, Aaron Short2, Tyler Nelson2
1Department of Pathology, Division of Neuropathology, The Ohio State University College of Medicine, Columbus, Ohio, 43210.
The Journal of Comparative Neurology
|July 16, 2016
Summary
Scaffold topography influences neural stem cell behavior. Fiber diameter impacts cell migration and morphology, demonstrating that the physical environment dictates cellular responses to proteins like laminin.
Area of Science:
- Neuroscience
- Biomaterials Science
- Cell Biology
Background:
- Neural stem cells (NSCs) navigate complex anatomical scaffolds in the central nervous system during development.
- Understanding how scaffold topography influences NSC behavior is crucial for regenerative medicine and neuroscience research.
- Previous work established polycaprolactone (PCL) fiber mats as topographically similar to brain scaffolds.
Purpose of the Study:
- To investigate the role of scaffold topography in directing neural stem cell migration and morphology.
- To mimic in vivo central nervous system scaffold features using electrospun PCL fibers of varying diameters.
- To compare NSC responses to large-diameter fibers (mimicking blood vessels) versus small-diameter fibers (mimicking radial glial processes).
Main Methods:
- Fabrication of electrospun PCL fiber mats with distinct fiber diameters to mimic different topographical environments.
- Culturing neural stem cells on these fiber mats with and without laminin.
- Assessing NSC migration, morphology (using fractal dimension), and response to cytoskeletal inhibitors (nocodazole, cytochalasin-D) and ROCK inhibitor.
Main Results:
- NSC migration and morphology were significantly influenced by topographical context and the presence of laminin.
- Large-fiber topography without laminin inhibited NSC migration, partially restored by ROCK inhibitor.
- Cell morphology complexity showed differential dependence on cytoskeletal proteins based on fiber topography, with nocodazole and cytochalasin-D affecting cells on large fibers but not small fibers.
Conclusions:
- Neural stem cell responses to laminin are dependent on the topographical context of the scaffold.
- Scaffold physical structure induces unique signaling cascades that regulate NSC migration and morphology.
- This study highlights the importance of biomimetic scaffold design for controlling neural stem cell behavior in vitro.
Keywords:
RRID: AB_2313773RRID: AB_305808RRID: AB_477010RRID: AB_531887RRID: AB_561007RRID: AB_628431RRID: SCR_001905RRID: SCR_002285RRID: SCR_013672RRID: SCR_014242RRID: SciRes_000136actincytoskeletonlamininmicrotubulesmigrationneural stem celltopographyMore Related Videos
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