Biomedical Engineering Reference
In-Depth Information
Self-renewal capacity
D
P
2
D
D
P
2
P
2
D
D
P
1
P
1
P
2
P
2
D
. . .
S
P
2
P
2
P
1
P
1
D
D
D
P
2
D
D
D
D
Differentiation level
Fig. 1
Schematic description of the cell hierarchy in a tissue. A stem (
S
) cell can replicate
indefinitely, while producing early progenitor cells (
P
1
), which in turn produce a larger population
of more differentiated progenitors (
P
2
). The differentiation process is naturally continuous and can
go on through several lineages of PCs, eventually resulting in fully differentiated (
D
) cells
cell that is more differentiated, termed a progenitor cell (PC). The PC transiently
amplifies, meaning that it replicates for a limited time. The PC produces either
additional PCs that are at an even more advanced stage of differentiation or
terminally differentiated cells (DCs), which cannot replicate (Fig.
1
). DCs fulfill the
tissue's functionality (e.g., blood cells, skin cells).
As noted above, the SC proliferation and differentiation rates must conform to
the tissue's development and changing needs. The SCs must constantly supply the
required quantities of DCs under various constraints, for example, in growing tissues
or following disease or injury. At the same time, the size of the SC population must
be restricted in order to prevent uncontrolled growth and crowding out of the DC
population and in order to decrease the risk of cancerous mutations [
7
].
Control over an SC's fate is exerted through the cell's microenvironment. The
SC receives signals from its environment and, according to these signals, “decides”
whether to replicate, differentiate, die (apoptosis), or remain quiescent. The signals
regulating SC decisions might come from any number of sources: they may be
determined by biochemical and mechanical characteristics of the environment, such
as cytokine concentrations, cell-to-cell signals, extracellular matrix properties, and
possibly somatic properties of the SC itself [
65
,
70
,
89
]. Some theories suggest that
an external, physical tissue structure transmits the various signals that regulate SC
fate [
14
]. Other theories propose that SCs are capable of sending signals to one
another without relying on additional structures. The QS theory, which forms the
basis of the work by Agur et al., stems from the latter approach.
The SC fate decision mechanism controls the cell-production rate, and this
control is key to tissue homeostasis. Derangement of this mechanism might lead to
the development of cancer. The theory of CSCs, elaborated in the following section,
creates an opportunity to further explore this notion.
Search WWH ::
Custom Search