Recent advances require a dual evaluation of germ and somatic stem cell niches with a regenerative medicine perspective. For a better point of view of the niche concept, it is needed to compare the microenvironments of those niches in respect to several components. The cellular environment of spermatogonial stem cells' niche consists of Sertoli cells, Leydig cells, vascular endothelial cells, epididymal fat cells, peritubular myoid cells while hematopoietic stem cells have mesenchymal stem cells, osteoblasts, osteoclasts, megacaryocytes, macrophages, vascular endothelial cells, pericytes and adipocytes in their microenvironment. Not only those cells', but also the effect of the other factors such as hormones, growth factors, chemokines, cytokines, extracellular matrix components, biomechanical forces (like shear stress, tension or compression) and physical environmental elements such as temperature, oxygen level and pH will be clarified during the chapter. Because it is known that the microenvironment has an important role in the stem cell homeostasis and disease conditions, it is crucial to understand the details of the microenvironment and to be able to compare the niche concepts of the different types of stem cells from each other, for the regenerative interventions. Indeed, the purpose of this chapter is to point out the usage of niche engineering within the further studies in the regenerative medicine field. Decellularized, synthetic or non-synthetic scaffolds may help to mimic the stem cell niche. However, the shared or different characteristics of germ and somatic stem cell microenvironments are necessary to constitute a proper niche model. When considered from this aspect, it is possible to produce some strategies on the personalized medicine by using those artificial models of stem cell microenvironment.