Abraham Jella-Andrea, Blaschke Stefan, Tarazi Samar, Dreissen Georg, Vay Sabine U, Schroeter Michael, Fink Gereon R, Merkel Rudolf, Rueger Maria A, Hoffmann Bernd
Mechanobiology, Institute of Biological Information Processing (IBI-2), Research Centre Juelich, Juelich, Germany.
Department of Neurology, Faculty of Medicine and University Hospital, University of Cologne, Cologne, Germany.
Front Cell Neurosci. 2021 Sep 24;15:706585. doi: 10.3389/fncel.2021.706585. eCollection 2021.
The neural stem cell (NSC) niche is a highly vascularized microenvironment that supplies stem cells with relevant biological and chemical cues. However, the NSCs' proximity to the vasculature also means that the NSCs are subjected to permanent tissue deformation effected by the vessels' heartbeat-induced pulsatile movements. Cultivating NSCs under common culture conditions neglects the-yet unknown-influence of this cyclic mechanical strain on neural stem cells. Under the hypothesis that pulsatile strain should affect essential NSC functions, a cyclic uniaxial strain was applied under biomimetic conditions using an in-house developed stretching system based on cross-linked polydimethylsiloxane (PDMS) elastomer. While lineage commitment remained unaffected by cyclic deformation, strain affected NSC quiescence and cytoskeletal organization. Unexpectedly, cyclically stretched stem cells aligned in stretch direction, a phenomenon unknown for other types of cells in the mammalian organism. The same effect was observed for young astrocytes differentiating from NSCs. In contrast, young neurons differentiating from NSCs did not show mechanoresponsiveness. The exceptional orientation of NSCs and young astrocytes in the stretch direction was blocked upon RhoA activation and went along with a lack of stress fibers. Compared to postnatal astrocytes and mature neurons, NSCs and their young progeny displayed characteristic and distinct mechanoresponsiveness. Data suggest a protective role of young astrocytes in mixed cultures of differentiating neurons and astrocytes by mitigating the mechanical stress of pulsatile strain on developing neurons.
神经干细胞（NSC）生态位是一个高度血管化的微环境，它为干细胞提供相关的生物和化学信号。然而，神经干细胞与脉管系统的接近也意味着神经干细胞会受到血管心跳引起的脉动运动所导致的永久性组织变形的影响。在普通培养条件下培养神经干细胞忽略了这种周期性机械应变对神经干细胞尚未明确的影响。基于脉动应变会影响神经干细胞基本功能的假设，使用内部开发的基于交联聚二甲基硅氧烷（PDMS）弹性体的拉伸系统，在仿生条件下施加周期性单轴应变。虽然谱系定向不受周期性变形的影响，但应变影响了神经干细胞的静止状态和细胞骨架组织。出乎意料的是，周期性拉伸的干细胞沿拉伸方向排列，这一现象在哺乳动物机体的其他类型细胞中并不为人所知。从神经干细胞分化而来的年轻星形胶质细胞也观察到了同样的效果。相比之下，从神经干细胞分化而来的年轻神经元没有表现出机械反应性。在RhoA激活后，神经干细胞和年轻星形胶质细胞在拉伸方向上的特殊排列被阻断，并且伴随着应力纤维的缺乏。与出生后星形胶质细胞和成熟神经元相比，神经干细胞及其年轻后代表现出独特的机械反应性。数据表明，在分化的神经元和星形胶质细胞的混合培养物中，年轻星形胶质细胞通过减轻脉动应变对发育中神经元的机械应力发挥保护作用。
