[Seminar] Mechanobio-materials manipulating motility and functions of stem cells by Prof. Satoru Kidoaki, Kyushu University

Dr. Satoru Kidoaki

Professor at Institute for Materials Chemistry and Engineering, Kyushu University

 

Mesenchymal stem cells (MSCs)  exhibit substrate stiffness-dependent differentiation, and history of the mechanical dose from culture environment essentially affects the fate of MSCs. In relation to this, we have found before that microelastically-patterned hydrogel with heterogeneous distribution  of matrix stiffness allow MSCs to suppress fate determination into specific lineages,  and contribute to keep the undifferentiated state. We call such mode of MSCs as in “frustrated differentiation”,  which serves to construct the culture substrate for MSCs to maintain their stemness in high-qualified state. The basis of this phenomenon is in the enforced oscillation of dose of mechanical signals from environment to MSCs during the nomadic movement between stiff and soft region of gel matrix, which would eliminate the history of experience on a certain level of stiffness.  To fully characterize the frustrated differentiation of MSCs, we have scrutinized the oscillation of mechanical dose and mechanical signal input to MSCs employing the long-term traction force microscopy on the microelastically-striped patterned gels. We have confirmed that the large degree of fluctuation of traction forces is the key factors to induce the frustrated differentiation of MSCs. In addition, DNA microarray experiments and pathway analyses were performed for the MSCs after the nomadic culture, and the gene expressions of APC, IGF2BP3, PIK3CA, and DUSP6 were found to significantly increase. Especially, APC is one of the critical regulators of Wnt signaling pathway controlling differentiation/undifferentiation state of stem cells. We discuss the mechanobiological effect of nomadic culture of MSCs in the filed of heterogenious elasticity on regulation of Wnt signaling.

 

1. T. Kawano and S. Kidoaki, Elasticity boundary conditions required for cell mechanotaxis on microelastically-patterned gels, Biomaterials, 32, 2725-2733 (2011).
2. T. Kuboki, F. Kantawong, R. Burchmore, M.J. Dalby, S. Kidoaki, 2D-DIGE proteomic analysis of mesenchymal stem cell cultured on the elasticity-tunable hydrogels, Cell Structure and Function, 37,127-139 (2012).
3. S. Kidoaki, H. Sakashita, Rectified cell migration on saw-like micro-elastically patterned hydrogels with asymmetric gradient ratchet teeth, PLOS One, 8(10), e78067 (2013).
4. T. Kuboki, W. Chen, S. Kidoaki, Time-dependent migratory behaviors in the long-term studies of fibroblast durotaxis on a hydrogel substrate fabricated with a soft band, Langmuir, 30, 6187-6196 (2014).
5. A. Ueki and S. Kidoaki, Manipulation of cell mechanotaxis by designing curvature of the elasticity boundary on hydrogel matrix, Biomaterials, 41, 45-52 (2015).
6. T. Kuboki and S. Kidoaki, Fabrication of elasticity-tunable gelatinous gel for mesenchymal stem cell culture, Methods Mol. Biol., 1416, 425-441 (2016).