| Autor: |
Madl CM; Department of Bioengineering, Stanford University, Stanford, California 94305, USA., LeSavage BL; Department of Bioengineering, Stanford University, Stanford, California 94305, USA., Dewi RE; Department of Materials Science & Engineering, Stanford University, Stanford, California 94305, USA., Dinh CB; Department of Materials Science & Engineering, Stanford University, Stanford, California 94305, USA., Stowers RS; Department of Mechanical Engineering, Stanford University, Stanford, California 94305, USA., Khariton M; Department of Bioengineering, Stanford University, Stanford, California 94305, USA., Lampe KJ; Department of Materials Science & Engineering, Stanford University, Stanford, California 94305, USA.; Department of Chemical Engineering, University of Virginia, Charlottesville, Virginia 22904, USA., Nguyen D; Department of Biology and Biological Engineering, Chalmers University of Technology, Gothenburg SE-412 96, Sweden., Chaudhuri O; Department of Mechanical Engineering, Stanford University, Stanford, California 94305, USA., Enejder A; Department of Materials Science & Engineering, Stanford University, Stanford, California 94305, USA.; Department of Biology and Biological Engineering, Chalmers University of Technology, Gothenburg SE-412 96, Sweden., Heilshorn SC; Department of Materials Science & Engineering, Stanford University, Stanford, California 94305, USA. |
| Abstrakt: |
Neural progenitor cell (NPC) culture within three-dimensional (3D) hydrogels is an attractive strategy for expanding a therapeutically relevant number of stem cells. However, relatively little is known about how 3D material properties such as stiffness and degradability affect the maintenance of NPC stemness in the absence of differentiation factors. Over a physiologically relevant range of stiffness from ∼0.5 to 50 kPa, stemness maintenance did not correlate with initial hydrogel stiffness. In contrast, hydrogel degradation was both correlated with, and necessary for, maintenance of NPC stemness. This requirement for degradation was independent of cytoskeletal tension generation and presentation of engineered adhesive ligands, instead relying on matrix remodelling to facilitate cadherin-mediated cell-cell contact and promote β-catenin signalling. In two additional hydrogel systems, permitting NPC-mediated matrix remodelling proved to be a generalizable strategy for stemness maintenance in 3D. Our findings have identified matrix remodelling, in the absence of cytoskeletal tension generation, as a previously unknown strategy to maintain stemness in 3D. |
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