Biomedical Engineering Reference
In-Depth Information
within the structure (Crittenden et al., 2002; Xie and Spradling, 2000; Kiger
et al., 2000). These experiments suggest that the niche contains heterologous
cell populations. Two studies in Drosophila showing that posterior mid-gut
cell populations yield daughter enterocytes and enteroendocrine raised the
controversy on whether there is need for other cell types for the functionality
of the niche. In these studies stem cells did not necessitate direct contact with
heterologous cells. Armadillo (a beta-catenin paralog) localized specifically
at the interface between stem cells (on the basement membrane separating
them from adjacent muscle cells) and their resulting enteroblasts. This sug-
gests that it is perhaps the basement membrane that provides a specific
microenvironment within the intestine. This microenvironment or niche is
composed of extracellular matrix and other non-cellular elements that in
unison control the cells within that niche without the necessity of heterolo-
gous cells. In mammalian skin, b-1 integrins have been found to be differen-
tially expressed on primitive cells and to engage in constrained localization of
a stem cell population via presumed crosstalk with matrix glycoprotein
ligands (Jones and Watt, 1993; Jensen et al., 1999). In the nervous system,
lack of Tenascin C changes neural stem cell number and function in the
subventricular zone (Garcion et al., 2004). In the blood system, deletion of
Tenascin C affects primitive cell populations, suggesting a role in the regula-
tion of hematopoietic stem (HS)-cell niches (Ohta et al., 1998). Osteopontin
(OPN), a matrix protein that is also involved in cell-mediated immunity and
metastasis, has recently been shown to play an important function in the
regulation of hematopoietic stem cell niches. OPNproduction fluctuates with
osteoblast activation, and animals deficient in OPN show an increased num-
ber of HS cells. OPN was shown to limit the number of stem cells under
homeostatic conditions or with stimulation, behaving as some sort of con-
straint regulating hematopoietic stem cells. In mammals examples of niches
include the identification of osteoblasts in the bone marrow compartment,
and the endothelium in the brain (Palmer et al., 2000; Calvi et al., 2003;
Zhang et al., 2003; Kiel et al., 2005). These studies show that extracellular
matrix components confer localizing niches that may provide stimulatory
and or inhibitory effects on the stem cells.
3.2 Paracrine Signals Within the Niche
The signals governing the physical organization of the niche are an important
component of the machinery of the niche. Experiments in mice have shown that
ephrins and their RTK receptors are mediators of structural boundaries and
they are involved in the organization of epithelial cells in the intestines. Anom-
alous expression of these molecules was found to lead to abnormal organization
of the crypt and the intestinal villus, affecting the stem cells contained within.
Wnt proteins as well as their antagonists regulate in a paracrine manner, to
