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.

中文翻译：

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维持3D水凝胶中神经祖细胞的干性需要基质重塑

三维（3D）水凝胶中的神经祖细胞（NPC）培养是扩大治疗相关数量的干细胞的一种有吸引力的策略。但是，关于3D材料属性（例如刚度和可降解性）如何在缺少分化因子的情况下如何影响NPC茎干维持的信息知之甚少。在生理相关的硬度范围内，从〜0.5到50 kPa，茎干维持率与初始水凝胶刚度不相关。相反，水凝胶降解既与维持NPC茎干有关，又是维持NPC茎干所必需的。降解的要求与细胞骨架张力的产生和工程化的粘合剂配体的表达无关，而是依赖于基质重塑来促进钙黏着蛋白介导的细胞间接触并促进β-catenin信号传导。在另外两个水凝胶系统中，允许NPC介导的基质重塑被证明是3D保持茎干的通用策略。我们的发现已将在没有细胞骨架张力产生的情况下进行基质重塑确定为维持3D干性的未知方法。