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. 2022 Jan 25;7(2):e10291.
doi: 10.1002/btm2.10291. eCollection 2022 May.

"Musical dish" efficiently induces osteogenic differentiation of mesenchymal stem cells through music derived microstretch with variable frequency

Qiulin He  1   2 , Junxin Lin  1   2 , Fanghao Zhou  3 , Dandan Cai  1   2 , Yiyang Yan  1   2 , Yejie Shan  3 , Shufang Zhang  1   2   4 , Tiefeng Li  3 , Xudong Yao  5 , Hongwei Ouyang  1   2   4   6
Affiliations

"Musical dish" efficiently induces osteogenic differentiation of mesenchymal stem cells through music derived microstretch with variable frequency

Qiulin He et al. Bioeng Transl Med. .

Abstract

Nonuniform microstretching (NUMS) naturally occurs in real bone tissues in vivo, but its profound effects have not been identified yet. In order to explore the biological effects of NUMS and static stretch (uniform stretch [US]) on cells, a new "musical dish" device was developed. Musical signal was used to provide NUMS to cells. More stress fibers, arranging along the long axis of cells, were formed throughout the cells under NUMS, compared with US and untreated control group, although cell morphology did not show any alteration. Whole transcriptome sequencing revealed enhanced osteogenic differentiation of cells after NUMS treatment. Cells in the NUMS group showed a higher expression of bone-related genes, while genes related to stemness and other lineages were down-regulated. Our results give insights into the biological effects of NUMS and US on stem cell osteogenic differentiation, suggesting beneficial effects of micromechanical stimulus for osteogenesis. The newly developed device provides a basis for the development of NUMS derived rehabilitation technology to promote bone healing.

Keywords: regenerative medicine; stem cell therapies; tissue engineering.

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Figures

FIGURE 1
FIGURE 1
Fabrication and strain characterization of the musical dish. (a) Schematics of the components in the musical dish. (b) The mechanism of cell stretching. (c) Picture of the musical dish. (d) Picture of the transparent electrode above a sheet with square lattice. (e,f) The static radial strain as a function of (e) applied voltage and (f) test number. (g,h) The cyclic radial strain under an alternating voltage between 0 V and 5 kV at (g) 0.15 Hz and (h) 1 Hz. Blue diamond: the average values of the maximum radial strains; orange square: the average values of the minimum radial strains; red circle: the difference between the maximum strains and the minimum strains
FIGURE 2
FIGURE 2
Model analysis of the homogeneity and equiaxiality of the musical dish. (a) Geometry and parameter definition. (b) The prestretch and Maxwell stress loading steps in the finite element analysis (FEA) simulation. (c) The contour of radial strain. (d) The contour of hoop strain. (e) The strain distribution along Path 1. (f) The strain distribution along Path 2
FIGURE 3
FIGURE 3
Fabrication and characterization of the musical dish culture system. (a) Diagram of musical dish culture system. (b) Pictures of musical dish at 0 and 4500 V. (c) Linear strain of musical dish from 0 to 5000 V. (d) CCK8 assay for cell proliferation in the musical dish and Petri dish groups between Days 1 and 5. (e) Phalloidin (red) and DAPI (blue) staining to show cell deformation under stretch by musical dish
FIGURE 4
FIGURE 4
The effect of stretch stimulation on cell morphology and cell cytoskeleton. (a) The relationship between stretching amplitude and time in the NUMS group. (b) The relationship between stretching frequency and intensity of the musical signal. (c,d) Cell area (c) and cell aspect ratio (d) analysis to show cell morphology in the nonuniform microstretching (NUMS), uniform stretch (US), and control group from Day 1 to Day 4 (N = 3, n > 8). (e,f) Phalloidin/DAPI staining (e) and quantitative analysis (f) to show cell cytoskeleton in the NUMS, US, and control group after stimulated for 6 h (N = 3, n = 6)
FIGURE 5
FIGURE 5
The effect of stretch stimulation on transcriptomic profiles. (a) Principal component analysis. (b) Venn diagram of differentially expressed genes (DEGs). (c) Heatmap of differentially expressed genes between the nonuniform microstretching (NUMS) and uniform stretch (US) groups. (d) Heatmap of differentially expressed genes between the NUMS and control groups. (e,f) Up‐regulated gene ontology (GO) terms between the NUMS and control groups (e), as well as the NUMS and US groups (f)
FIGURE 6
FIGURE 6
The effect of stretch stimulation on cell differentiation. (a–e) Q‐PCR analysis of the expression level of genes related to stemness (a,b), chondrogenesis (c), adipogenesis (d) and osteogenesis (e) after stimulation (N = 3, n = 3). (f,g) Q‐PCR analysis of the expression level of genes related to osteogenesis after osteogenic induction (N = 3, n = 3). (h,i) Alizarin red staining (h) and quantitative analysis (i) after osteogenic induction (N = 3, n = 3)
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