Strain and Vibration in Mesenchymal Stem Cells

Abstract

Mesenchymal stem cells (MSCs) are multipotent cells capable of differentiating into any mesenchymal tissue, including bone, cartilage, muscle, and fat. MSC differentiation can be influenced by a variety of stimuli, including environmental and mechanical stimulation, scaffold physical properties, or applied loads. Numerous studies have evaluated the effects of vibration or cyclic tensile strain on MSCs towards developing a mechanically based method of differentiation, but there is no consensus between studies and each investigation uses different culture conditions, which also influence MSC fate. Here we present an overview of the response of MSCs to vibration and cyclic tension, focusing on the effect of various culture conditions and strain or vibration parameters. Our review reveals that scaffold type (e.g., natural versus synthetic; 2D versus 3D) can influence cell response to vibration and strain to the same degree as loading parameters. Hence, in the efforts to use mechanical loading as a reliable method to differentiate cells, scaffold selection is as important as method of loading.

Figure 1

Diagram representing the effects of vibration (blue jagged arrow) and cyclic tensile strain (green squiggly arrow) on MSCs. The arrows depict the loading type. The italics detail the in vitro culture conditions in which the differentiation into the indicated lineage was observed. Red lines indicate inhibition of the downstream lineage. Tissue images from Tuan et al. [4], CC BY 4.0.

Figure 2

Acoustic-frequency vibratory stimulation (AFVS) modulates expression of mRNA encoding osteogenesis-specific markers in human bone marrow-derived mesenchymal stem cells (BM-MSCs) at the time points of day 7 ((a), (b), (c), and (d)) and day 14 ((e), (f), (g), and (h)). The mRNA levels of COL1A1 ((a), (e)), ALP ((b), (f)), RUNX2 ((c), (g)), and SPP1 ((d), (h)) were measured by real-time RT-PCR. Values are mean ± standard error of four independent experiments (n = 4). ^∗P < 0.05; ^∗∗P < 0.01 in the indicated groups from unpaired t-test. ^#P < 0.01; ^##P < 0.01 compared with the 0 Hz control group from unpaired t-test. From Chen et al. [10], CC BY 3.0.

Figure 3

Effect of microvibration on osteogenic gene expressions in BMSC cellular scaffolds. Cbfa1/Runx2, Col I, ALP, and OC mRNA expressions were assayed on days 1, 4, 7, 10, 14, 18, 22, and 26. Data show that microvibration greatly upregulated these mRNA levels at different stages of osteogenesis. Each bar represents the mean ± standard deviation (n = 3); ^∗P < 0.05. SC, static culture. MC, microvibration culture. Col I, collagen I. ALP, alkaline phosphatase. OC, osteocalcin. From Zhou et al., [17] with kind permission from eCM journal (http://www.ecmjournal.org).

Figure 4

Effects of uniaxial strain on SM marker expression in MSCs. MSCs were cultured on collagen-coated elastic membranes for 1 day and subjected to 10% uniaxial strain at 1 Hz or kept as static controls for 1 and 2 days. (a) The RNA from each sample was reverse-transcribed into cDNA and the gene expression of SM a-actin, SM-22a, and GAPDH was analyzed by qPCR with their respective primers. The expression level of each gene was normalized with the level of GAPDH in the same sample. The ratio of the gene expression (stretch/static) is presented as mean (±) standard deviation from at least three experiments. ^∗Significant difference (P < 0.05) from 1. (b) The protein expression of SM a-actin and actin was analyzed by immunoblotting with respective antibody. (c) Statistical analysis of protein expression. The protein expression was quantified, and the expression level of a-actin was normalized with the level of h-actin in the same samples. The ratio of the normalized protein expression (stretch/static) is presented as mean (±) standard deviation from at least three experiments. From Park et al., Biotechnology and Bioengineering [20]. Copyright© 2004 by John Wiley Sons, Inc. Reprinted by permission of John Wiley & Sons, Inc.