Abstract

Self-renewal and differentiation are two fundamental characteristics of stem cells. Stem cell self-renewal is critical for replenishing the stem cell population, while differentiation is necessary for maintaining tissue homeostasis. Over the last two decades a great deal of effort has been applied to discovering the processes that control these opposing stem cell fates. One way of examining the role of the physical environment is the use of biomaterial strategies that have the ability to manipulate cells without any requirement for chemical factors. The mechanism whereby cells have been found to respond to a mechanical stimulus is termed mechanotransduction, the process by which a mechanical cue (or alteration in cell spreading changing internal cellular mechanics, i.e. intracellular tension) is transduced into a chemical signal inside the cell, eliciting changes in gene expression. This can occur either directly, as a result of changes in the cell cytoskeleton, or indirectly through a series of biochemical signalling cascades. The main focus of this review is to examine the role of mechanotransduction in the differentiation and self-renewal of stem cells. In particular, we will focus on the use of biomaterials as a tool for examining mechanotrandsuctive effects on self-renewal and differentiation.

Highlights

  • Stem cellsThere are different types of stem cells, including adult (e.g. mesenchymal stem cells, MSCs), embryonic (ESCs) and inducible pluripotent (iPSCs)

  • There are different types of stem cells, including adult, embryonic (ESCs) and inducible pluripotent

  • Physical components include the interaction of stem cells with other cell types, the basement membrane and extracellular matrix (ECM), whilst intrinsic and extrinsic signalling from other cells within and outwith the niche, as well as neural and metabolic signalling, can serve as regulators of self-renewal or differentiation (Li and Xie, 2005; Scadden, 2006)

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Summary

Stem cells

There are different types of stem cells, including adult (e.g. mesenchymal stem cells, MSCs), embryonic (ESCs) and inducible pluripotent (iPSCs). Pluripotent stem cells can be produced following viral transfection of a terminally differentiated cell, using four key genes, Oct (Pou5f1), Sox, cMyc and Klf. Pluripotent stem cells can be produced following viral transfection of a terminally differentiated cell, using four key genes, Oct (Pou5f1), Sox, cMyc and Klf4 They provide us with the potential to address the issues of achieving increases in pluripotency and accessibility. Over the last decade, researchers have shown that the sole use of nanotopography can induce differentiation without the need for supplements for specific media (Engler et al, 2006, Dalby et al, 2007c) This is an important issue when culturing cells with the potential to be transplanted into patients

The stem cell niche
Stem cell division
Cell cycle control of self-renewal and differentiation
Biomaterial control of stem cell self-renewal and differentiation
Chemistry
Topography
Elasticity
Cell–extracellular matrix adhesions
Integrin-mediated mechanotransduction
Integrins and the cell cycle
Integrins and stem cell division
Mechanotransduction and the primary cilium
Dynamic surfaces
Summary
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