Abstract
BackgroundMechanical stimuli play important roles in the proliferation and differentiation of adult stem cells. However, few studies on their effects on induced pluripotent stem cells (iPSCs) have been published.MethodsHuman dermal fibroblasts were seeded onto flexible membrane-bottom plates, and infected with retrovirus expressing the four reprogramming factors OCT4, SOX2, KLF, and c-MYC (OSKM). The cells were subjected to equiaxial stretching (3% or 8% for 2, 4, or 7 days) and seeded on feeder cells (STO). The reprogramming into iPSCs was evaluated by the expression of pluripotent markers, in vitro differentiation into three germ layers, and teratoma formation.ResultsEquiaxial stretching enhanced reprogramming efficiency without affecting the viral transduction rate. iPSCs induced by transduction of four reprogramming factors and application of equiaxial stretching had characteristics typical of iPSCs in terms of pluripotency and differentiation potentials.ConclusionsThis is the first study to show that mechanical stimuli can increase reprogramming efficiency. However, it did not enhance the infection rate, indicating that mechanical stimuli, defined as stretching in this study, have positive effects on reprogramming rather than on infection. Additional studies should evaluate the mechanism underlying the modulation of reprogramming of somatic cells into iPSCs.
Highlights
Mechanical stimuli play important roles in the proliferation and differentiation of adult stem cells
One study showed that only three reprogramming factors (OCT4, Sex determining region Y-box 2 (SOX2), Kruppel-like factor 4 (KLF4)), excluding c-MYC, enabled mouse or human somatic cells to be reprogrammed into Induced pluripotent stem cell (iPSC), resulting in a decrease in tumor formation compared to reprogramming with the four factors [9]
Qualitative and quantitative analyses (Fig. 3b and c), using green fluorescent protein (GFP) fluorescence images and Fluorescence-activated cell sorting (FACS), revealed lower infection efficiencies when the cells were on flexible membranes than when on commercial culture plates
Summary
Mechanical stimuli play important roles in the proliferation and differentiation of adult stem cells. Few studies on their effects on induced pluripotent stem cells (iPSCs) have been published. One study showed that only three reprogramming factors (OCT4, SOX2, KLF4), excluding c-MYC, enabled mouse or human somatic cells to be reprogrammed into iPSCs, resulting in a decrease in tumor formation compared to reprogramming with the four factors [9]. These safety problems require extensive further investigation and resolution
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