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Review
. 2018 Sep;75(18):3297-3312.
doi: 10.1007/s00018-018-2830-z. Epub 2018 May 4.

Why the impact of mechanical stimuli on stem cells remains a challenge

Roman Goetzke  1   2 , Antonio Sechi  2 , Laura De Laporte  3 , Sabine Neuss  4   5 , Wolfgang Wagner  6   7   8
Affiliations
Review

Why the impact of mechanical stimuli on stem cells remains a challenge

Roman Goetzke et al. Cell Mol Life Sci. 2018 Sep.

Abstract

Mechanical stimulation affects growth and differentiation of stem cells. This may be used to guide lineage-specific cell fate decisions and therefore opens fascinating opportunities for stem cell biology and regenerative medicine. Several studies demonstrated functional and molecular effects of mechanical stimulation but on first sight these results often appear to be inconsistent. Comparison of such studies is hampered by a multitude of relevant parameters that act in concert. There are notorious differences between species, cell types, and culture conditions. Furthermore, the utilized culture substrates have complex features, such as surface chemistry, elasticity, and topography. Cell culture substrates can vary from simple, flat materials to complex 3D scaffolds. Last but not least, mechanical forces can be applied with different frequency, amplitude, and strength. It is therefore a prerequisite to take all these parameters into consideration when ascribing their specific functional relevance-and to only modulate one parameter at the time if the relevance of this parameter is addressed. Such research questions can only be investigated by interdisciplinary cooperation. In this review, we focus particularly on mesenchymal stem cells and pluripotent stem cells to discuss relevant parameters that contribute to the kaleidoscope of mechanical stimulation of stem cells.

Keywords: Biomaterials; Embryonic stem cells; Epigenetic; Hydrogels; Induced pluripotent stem cells; Matrix; Mechanobiology; Mesenchymal stromal cells; Soft; iPSC.

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Conflict of interest statement

The authors declare no competing financial interests.

Figures

Fig. 1
Fig. 1
Hallmarks of mechanobiology. Stem cells sense and respond to various different biomaterial properties (including topography, elasticity, 3D environment, and surface chemistry) and mechanical stimulation (e.g. compression, stretching, or shear stress). In addition, timing and cell-intrinsic mechanisms for mechanosensing are relevant for the cellular response
Fig. 2
Fig. 2
Effects of matrix elasticity may be transient while the cells are cultured on the substrate. a MSC were isolated from bone marrow and continuously culture expanded on either tissue culture plastic (TCP) or polydimethylsiloxane (PDMS) with different elastic moduli. Osteogenic and adipogenic differentiation was then induced on the substrates and analysed by semiquantitative analysis of calcium phosphate precipitates and the percentage of cells with lipid-droplets, respectively. Osteogenic differentiation was enhanced on stiff substrates, whereas adipogenic differentiation was more pronounced on softer materials (*p < 0.05). b However, if MSC were continuously cultured on the substrates as indicated and then re-seeded on TCP before induction of in vitro differentiation, the above-mentioned propensity of lineage-specific differentiation was not observed. Additional information on these results is provided in Schellenberg et al. [44]. c MSC and iPSC-derived MSC were generated in parallel on TCP and a very soft hydrogel of human platelet lysate. Unexpectedly, the different culture conditions hardly evoked significant differences in global gene expression analysis. The number of significant transcripts is indicated (adjusted p value < 0.05). Further details are provided in Goetzke et al. [61]
Fig. 3
Fig. 3
Grooves affect morphology of single iPSC and of iPSC colonies. Confocal microscopy images of single iPSC (a) and iPSC colonies (b) seeded on PDMS substrates structured with grooves of different periodicities (nm periodicity is indicated). Cells were stained for actin (green) and nuclei (blue). The dotted white arrow always indicates the direction of the sub-micron grooves. Scale bars = 20 µm for (a) and 50 µm for (b). Further details are provided in Abagnale et al. [83]
Fig. 4
Fig. 4
Exemplary depiction of mechanosensing pathways. Interaction of cells with the extracellular matrix is mediated through α/β-integrin heterodimers. It has been shown that integrins are involved in activating RhoA signaling (amongst other potential pathways), which in turn leads to acto-myosin contractility. The linker of nucleoskeleton and cytoskeleton (LINC) complex interacts with the actin cytoskeleton leading to nuclear lamin A-mediated DNA replication, alterations in gene expression, or epigenetic changes in the nucleus
See this image and copyright information in PMC

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