Biomedical Engineering Reference
In-Depth Information
(A)
(B)
EMS
SEI
4.0 kV ×50.000
100 mm WD9.0 mm
(D)
(C)
Figure 3.3
Natural ECMs of varying tissues. (A) 4′,6-Diamidino-2-phenylindole (DAPI) nuclei
staining shower arrangement of cells in ECM of neural tubes [63]. (B) Scanning electron microscopy
(SEM) image of an osteoblast cell in ECM [64]. (C) Staining reveals arrangement of neural stem cells
in the subventricular zone around a blood vessel [65]. (D) Aligned fibroblasts and myocytes in cardiac
tissue [66].
(See insert for color representation of the figure.)
Chemical Properties of the ECM
The key to understanding how stem cells operate is understanding their niche environment;
the surrounding microenvironment that regulates all aspect of stem-cell function, including
survival, self-renewal, and differentiation. Niches are tissue specific, and while they gener-
ally have similar components, variations directly affect the type of stem cell that is supported
by a specific environment (Figure 3.1). The ECM is primarily composed of collagen, lam-
inin, and fibronectin, and also elastin, fibrillin, tenascin, glycosaminoglycans, and proteo-
glycans [13]. Within the niche, stem cells are exposed to ECM molecules, as well as a
homeostatic gradient of soluble chemokines, cytokines, and growth factors. Some of the
most important parts of the niche are growth factors, which may be either soluble or bound
to the ECM. When added to culture, or secreted by either stem cells or other niche cells, they
often have potent effects on the stem cells. Thus, growth factors are highly regulated
in vivo
,
both in space and time [14].
When culturing stem cells, one way to control niche interactions is to use two-dimensional
patterning to create a secluded island of ECM, which affects diffusion patterns of secreted
growth factors and inhibits effects of both the matrix and cellular contacts [15]. Peerani
