Nanotopography - potential relevance in the stem cell niche.

Understanding signals in the niche that regulate stem cell behaviours is important for applications such as tissue engineering, and limitations in ex vivo/in vitro recapitulation of some stem cell niches, particularly the bone marrow, have led researchers to attempt to delineate signalling mechanisms present in vivo using a reductionist approach. This is especially important as 'stemness' is not solely an intrinsic property of stem cells but a result of the reciprocal interactions between stem cells and their niches. Physical stimuli such as mechanical stiffness and topography are known to significantly impact stem cell behaviours; being translated through adhesions, intracellular tension and mechanotransduction, which can alter gene expression and thus cell fate. In this review general properties of the stem cell niche are initially described, using intestinal and bone marrow niches as examples. The lesser-described physical stimuli of nanotopography and the mechanisms by which stem cells respond and interact with it are described, including biochemical and physical mechanotrasduction, chemical and physical signal integration and adhesion mechanisms in both anchorage-dependent and -independent cells. Specific examples of nanotopographical influence over stem cell differentiation are highlighted and parallels drawn between the stem cell niche and these 'synthetic'in vitro observations. Ultimately if the complex stem cell niche is to be mimicked in vitro or stem cells exploited for medical applications the physical microenvironment, including nanotopography, must be optimised.