The use of material properties to guide cell behaviour is often utilised in the field of regenerative medicine. Regarding this, surface topography has been shown to control different cellular processes. In nature, topographies exist in a wide variety of shapes, including hierarchical structures with a great degree of surface roughness. Here, inspired by nature, the potential of such surface characteristics in guiding cell behaviour was investigated via replication of 32 natural surfaces onto polystyrene using hot embossing techniques. Fluorescent image analysis of bone marrow-derived human mesenchymal stem cells cultured on these surfaces showed that cell shape was greatly affected by the distinct topographical features compared to a flat surface. Cluster analysis identified groups showing similar effect on nuclear and cell morphological parameter such as size, orientation and compactness. Related to this, focal adhesion formation and organisation was highly dependent on surface topography. Namely, focal adhesion maturation was promoted on the natural topographies. Furthermore, mouse embryonic stem cell pluripotency and colony morphology was influenced by natural topographies. Finally, natural topographies modulated in vitro mesenchymal stem cell differentiation. This study shows the capability of natural topographies to regulate cell behaviour useful for regenerative applications.