Laboratory of Cardiovascular Biology, IRCCS Ospedale Policlinico San Martino, Viale Rosanna Benzi 10, 16132 Genova, Italy.
National Laboratory of Molecular Biology and Stem Cell Bioengineering of the National Institute of Biostructures and Biosystems (NIBB)-Eldor Lab, Innovation Accelerator, CNR, Via Piero Gobetti 101, 40129 Bologna, Italy.
Cells. 2022 May 12;11(10):1629. doi: 10.3390/cells11101629.
Cytoskeletal proteins provide architectural and signaling cues within cells. They are able to reorganize themselves in response to mechanical forces, converting the stimuli received into specific cellular responses. Thus, the cytoskeleton influences cell shape, proliferation, and even differentiation. In particular, the cytoskeleton affects the fate of mesenchymal stem cells (MSCs), which are highly attractive candidates for cell therapy approaches due to their capacity for self-renewal and multi-lineage differentiation. Cytochalasin B (CB), a cyto-permeable mycotoxin, is able to inhibit the formation of actin microfilaments, resulting in direct effects on cell biological properties. Here, we investigated for the first time the effects of different concentrations of CB (0.1-10 μM) on human adipose-derived stem cells (hASCs) both after 24 h (h) of CB treatment and 24 h after CB wash-out. CB influenced the metabolism, proliferation, and morphology of hASCs in a dose-dependent manner, in association with progressive disorganization of actin microfilaments. Furthermore, the removal of CB highlighted the ability of cells to restore their cytoskeletal organization. Finally, atomic force microscopy (AFM) revealed that cytoskeletal changes induced by CB modulated the viscoelastic properties of hASCs, influencing their stiffness and viscosity, thereby affecting adipogenic fate.
细胞骨架蛋白在细胞内提供结构和信号线索。它们能够响应机械力重新组织自身，将接收到的刺激转化为特定的细胞反应。因此，细胞骨架影响细胞的形状、增殖，甚至分化。特别是，细胞骨架影响间充质干细胞（MSCs）的命运，由于其自我更新和多谱系分化的能力，MSCs 是细胞治疗方法的极具吸引力的候选者。细胞松弛素 B（CB）是一种细胞通透性真菌毒素，能够抑制肌动蛋白微丝的形成，从而对细胞生物学特性产生直接影响。在这里，我们首次研究了不同浓度的 CB（0.1-10 μM）在 CB 处理 24 小时（h）后和 CB 洗脱 24 小时后对人脂肪来源干细胞（hASC）的影响。CB 以剂量依赖性方式影响 hASC 的代谢、增殖和形态，与肌动蛋白微丝的逐渐解聚有关。此外，CB 的去除突出了细胞恢复细胞骨架组织的能力。最后，原子力显微镜（AFM）显示，CB 诱导的细胞骨架变化调节了 hASC 的粘弹性特性，影响其刚度和粘度，从而影响脂肪生成命运。
