Acoustic tweezing cytometry enhances osteogenesis of human mesenchymal stem cells through cytoskeletal contractility and YAP activation.
Acoustic tweezing cytometry enhances osteogenesis of human mesenchymal stem cells through cytoskeletal contractility and YAP activation.
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DOI：
10.1016/j.biomaterials.2017.04.039
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发表时间：
2017-07
期刊：
影响因子：
14
通讯作者：
Fu J
中科院分区：
文献类型：
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作者：
Xue X;Hong X;Li Z;Deng CX;Fu J
人骨髓间充质干细胞（hMSCs）在以细胞为基础的治疗退行性骨疾病方面具有巨大的潜力。已知细胞微环境中的机械信号在调节hMSCs的成骨（骨）分化中起重要作用。然而，由于hMSC培养的复杂生物材料设计标准，在常规二维（2D）单一培养物或生物工程三维（3D）组织构建物中hMSC谱系定型的机械调节仍然是次优的。在这项研究中，我们证明了一种新的细胞力学和机械生物学工具，声钳流式细胞术（ATC）的可行性，机械刺激的hMSCs。ATC利用超声（US）脉冲来驱动功能化的脂质微泡（MB），所述功能化的脂质微泡通过整合素结合共价连接到hMSC以向细胞施加力。ATC刺激增加hMSCs的细胞骨架收缩性，与细胞面积无关。此外，ATC应用在本质上抑制hMSC成骨的培养条件下挽救了hMSC的成骨分化（例如，软细胞培养表面）。ATC应用激活转录调节因子雅普以增强hMSC成骨。我们的数据进一步表明，F-肌动蛋白，肌球蛋白II，和RhoA/ROCK信号传导功能上游的雅普活性介导的ATC刺激的hMSC成骨。由于能够对细胞施加受控的动态机械刺激，ATC为组织工程和再生医学应用中的干细胞行为的机械调节提供了强有力的工具。
Human mesenchymal stem cells (hMSCs) have great potential for cell-based therapies for treating degenerative bone diseases. It is known that mechanical cues in the cell microenvironment play an important role in regulating osteogenic (bone) differentiation of hMSCs. However, mechanoregulation of lineage commitment of hMSCs in conventional two-dimensional (2D) monocultures or bioengineered three-dimensional (3D) tissue constructs remains suboptimal due to complex biomaterial design criteria for hMSC culture. In this study, we demonstrate the feasibility of a novel cell mechanics and mechanobiology tool, acoustic tweezing cytometry (ATC), for mechanical stimulation of hMSCs. ATC utilizes ultrasound (US) pulses to actuate functionalized lipid microbubbles (MBs) which are covalently attached to hMSCs via integrin binding to exert forces to the cells. ATC stimulation increases cytoskeletal contractility of hMSCs regardless of the cell area. Furthermore, ATC application rescues osteogenic differentiation of hMSCs in culture conditions that are intrinsically repressive for hMSC osteogenesis (e.g., soft cell culture surfaces). ATC application activates transcriptional regulator YAP to enhance hMSC osteogenesis. Our data further show that F-actin, myosin II, and RhoA/ROCK signaling function upstream of YAP activity in mediating ATC-stimulated hMSC osteogenesis. With the capability of applying controlled dynamic mechanical stimuli to cells, ATC provides a powerful tool for mechanoregulation of stem cell behaviors in tissue engineering and regenerative medicine applications.
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DOI：
10.1073/pnas.0903269107
发表时间：
2010-03-16
影响因子：
11.1
作者：
Kilian, Kristopher A.;Bugarija, Branimir;Mrksich, Milan
通讯作者：
Mrksich, Milan
影响因子：
3.4
作者：
Chen, Di;Sun, Yubing;Fu, Jianping
通讯作者：
Fu, Jianping
影响因子：
56.9
作者：
Hong, JH;Hwang, ES;Yaffe, MB
通讯作者：
Yaffe, MB
影响因子：
41.2
作者：
Sun, Yubing;Yong, Koh Meng Aw;Villa-Diaz, Luis G.;Zhang, Xiaoli;Chen, Weiqiang;Philson, Renee;Weng, Shinuo;Xu, Haoxing;Krebsbach, Paul H.;Fu, Jianping
通讯作者：
Fu, Jianping
影响因子：
41.2
作者：
通讯作者：
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