In the adult mammalian organism, hematopoietic stem cells (HSCs) reside primarily in the bone marrow (BM) and are the source for regeneration of all immune and blood cells. Recent progress in biotechnology and biomaterials science has fostered engineering approaches to explore the niche concept by means of bioartificial concepts in vitro. This chapter focuses on an introduction to existing HSC niche concepts and summarizes approaches to mimic them in an experimental manner ex vivo. It illustrates a few examples, showing their ability to mimic relevant features of in vivo stem cell behavior, and highlights the early approaches of HSC culture and HSC expansion. Additionally, a more complex setup of adhesion ligands and growth factors presentations as well as coculture systems is discussed.