“…Several different approaches to culture and investigate HSCs in vitro using 3D systems have been tested up until now: HSCs †, § have been encapsulated in hydrogels made of natural (e.g., collagen, hyaluronic acid) or synthetic (e.g., polyacrylates) monomers; 48,50,52 Other approaches included seeding of HSCs † onto scaffolds made of fibres or fibre meshworks, 51 as well as culturing HSCs †, ‡ ‡ in macroporous scaffolds that resemble the spongy architecture of trabecular bones 49,[181][182][183] (these host the red, blood-forming bone marrow); Furthermore, microwell-arrays have been used as quasi-or pseudo-3D environments for HSCs § §, ¶ ¶ in order to delineate signals and parameters that are present in the HSC niche. [184][185][186][187] All of these studies showed that HSCs respond and act differently in 3D materials than in standard 2D culture, backing the assumption that conventional 2D culture is a highly artificial situation for HSCs, which may even induce 'unnatural' cell behaviour.…”