Cell adhesion and mechanical stimulation in the regulation of mesenchymal stem cell differentiation (original) (raw)
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The understanding of the cytoskeleton's importance in stem cells is essential for their manipulation and further clinical application. The cytoskeleton is crucial in stem cell biology and depends on physical and chemicals signals to define its structure. Additionally, cell culture conditions will be important in the proper maintenance of stemness, lineage commitment and differentiation. This review focuses on the role of the actin cytoskeleton of stem cells during differentiation, the significance of cellular morphology, signaling pathways involved in cytoskeletal rearrangement in stem cells, the mechanobiology and mechanotransduction processes implicated in the interactions of stem cells with different surfaces of biomaterials, such as the nanotopography which is a physical cue influencing the differentiation of stem cells. Also, cancer stem cells are included since it is necessary to understand the role of their mechanical properties to develop new strategies to treat cancer. In this context, to study the stem cells requires integrated disciplines, including molecular and cellular biology, chemistry, physics, immunology, but also mechanobiology. Finally, as one of the purposes of stem cells is their application in regenerative medicine, their deepest understanding is necessary in order to establish safety protocols and effective cell-based therapies.
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Stem cells interact with and respond to a myriad of signals emanating from their extracellular microenvironment. The ability to harness the regenerative potential of stem cells via a synthetic matrix has promising implications for regenerative medicine. Electrospun fibrous scaffolds can be prepared with high degree of control over their structure creating highly porous meshes of ultrafine fibers that resemble the extracellular matrix topography, and are amenable to various functional modifications targeted towards enhancing stem cell survival and proliferation, directing specific stem cell fates, or promoting tissue organization. The feasibility of using such a scaffold platform to present integrated topographical and biochemical signals that are essential to stem cell manipulation has been demonstrated. Future application of this versatile scaffold platform to human embryonic and induced pluripotent stem cells for functional tissue repair and regeneration will further expand its potential for regenerative therapies.
The Control of Mesenchymal Stromal Cell Osteogenic Differentiation through Modified Surfaces
Stem cells international, 2013
Stem cells continue to receive widespread attention due to their potential to revolutionise treatments in the fields of both tissue engineering and regenerative medicine. Adult stem cells, specifically mesenchymal stromal cells (MSCs), play a vital role in the natural events surrounding bone healing and osseointegration through being stimulated to differentiate along their osteogenic lineage and in doing so, they form new cortical and trabecular bone tissue. Understanding how to control, manipulate, and enhance the intrinsic healing events modulated through osteogenic differentiation of MSCs by the use of modified surfaces and biomaterials could potentially advance the fields of both orthopaedics and dentistry. This could be by either using surface modification to generate greater implant stability and more rapid healing following implantation or the stimulation of MSCs ex vivo for reimplantation. This review aims to gather publications targeted at promoting, enhancing, and controll...
Harnessing traction-mediated manipulation of the cell/matrix interface to control stem-cell fate
Nature Materials, 2010
Stem cells sense and respond to the mechanical properties of the extracellular matrix. However, both the extent to which extracellular-matrix mechanics affect stem-cell fate in three-dimensional microenvironments and the underlying biophysical mechanisms are unclear. We demonstrate that the commitment of mesenchymal stem-cell populations changes in response to the rigidity of three-dimensional microenvironments, with osteogenesis occurring predominantly at 11-30kPa. In contrast to previous two-dimensional work, however, cell fate was not correlated with morphology. Instead, matrix stiffness regulated integrin binding as well as reorganization of adhesion ligands on the nanoscale, both of which were traction dependent and correlated with osteogenic commitment of mesenchymal stem-cell populations. These findings suggest that cells interpret changes in the physical properties of adhesion substrates as changes in adhesion-ligand presentation, and that cells themselves can be harnessed as tools to mechanically process materials into structures that feed back to manipulate their fate.