Microenvironment Design for Stem Cell Fate Determination - Tissue Engineering: Cell-Surface Interactions for Tissue Culture - page 230

Fig. 2 Schematic model of the bone marrow stem cell microenvironment, also termed ''bone
marrow niche'' (reprinted by permission from [ 5 ])
environment. Experimental evidence suggests that specific signaling pathways,
such as Notch and Wnt, are activated in the BM and may have a role in HSC
regulation [ 12 ].
Despite the success in identifying some of the components and signals of the
HSC niche, a complete understanding of the mechanisms involved in HSC regu-
lation still remains elusive, also due to the limited availability of appropriate ex
vivo models which could mimic the complex niche organization. Cell culture
systems developed so far do not entirely reproduce the physiological signals
required to establish a functional niche structure, resulting in a limited efficiency in
maintaining long-term repopulation of HSCs in vitro. Nevertheless, recent studies
indicate the potential of three-dimensional (3D) scaffold-based perfusion systems
as a suitable cultivation model for reconstructing ex vivo the BM stem cell niche,
supporting HSC long-term expansion [ 13 ].
The bone marrow microenvironment houses an additional stem cell population,
the BM-derived MSCs. These multipotent cells retain differentiation capabilities
along a number of different mesenchymal lineages, including bone, cartilage, fat,
tendon and muscle [ 14 , 15 ]. Their differentiation has been shown to be manipu-
lated exclusively in response to specific culture conditions; hence, in theory, they
may serve as an ideal alternative to fully differentiated mesodermal cells [ 14 ].
Moreover, recent studies have indicated that these cells not only differentiate into
mesodermal cells, but can also adopt the fate of endodermal and ectodermal cell