Biomedical Engineering Reference
In-Depth Information
Stem
Cell
Early
Progenitor
Late
Progenitor
Precursor
Cell
Mature
Cell
Potential 2
30
to
2
50
per cell
Need About
10
16
total over
lifetime
Cell
Number
Very slow
(t
d
~ 1/6wks.)
Slow
(t
d
~60-100 hrs.)
Very rapid
(t
d
~ 12 hrs.)
Slow
Zero
(can be activated
in special cases)
Cell
Cycling
Very Active
(1:5,000 survives)
Slow
Inactive
Inactive
Inactive
(can be induced)
Apoptosis
Function of
Physiological
State
Zero
Low
Higher
Zero
(except during
homing)
Motility
Cell-Cell
Contact
Cell-Cell
Contact
Soluble
Growth Factors
Soluble
Growth Factors
Soluble
Growth Factors
Regulation
FIGURE 6.9
Model for cell production in prolific tissues. This model was derived from decades-long research
in hematology. The columns represent increasingly differentiated cells, while the rows indicate the cellular fate
processes (Figure 16.4) and other events that cells undergo at different states of differentiation. (
t
d
denotes doubling
time.)
and in others by matrix and/or soluble signals in their microenvironment. The microenvi-
ronment can include signaling affecting growth, differentiation, or
apoptosis.
For example,
some growth factors are survival factors with antiapoptotic effects.
Examples of Stem Cell-Fed Maturational Lineages
The stem cell models best characterized are the hemopoietic stem cells, the intestinal
stem cells, and the skin stem cells. In addition, bone marrow-derived mesenchymal stem
cells and stem cells of the liver are being increasingly investigated. These systems are
described further in the following sections.
Bone Marrow and Blood Cell Formation
Hematopoiesis
was the first tissue function for which a stem cell model was established
(see Figure 6.3). The reconstitution of the multiple lineages of hematopoietic cells following
a stem cell transplant in mice has been demonstrated to occur with a surprisingly small
number of cells. Once the cells have reached certain maturational stages, they leave the
bone marrow and enter the circulation, where they perform their mature cell functions.
The mature cells eventually die and must be replaced. The rate of death of mature cells
(by apoptosis or necrosis) sets the need for the cell production rate in the tissue. Ultimately,
this death rate determines the number of stem cell commitments that are required. The
specific hematopoietic lineage cell production is given in Figure 6.3.
The Villi in the Small Intestine
The lining of the small intestine is comprised of villi that absorb nutrients, as shown in
Figure 6.10. The intestinal epithelial cell layer is highly dynamic. Its cellular content turns
over approximately every five days and is a very prolific tissue. In between the villi are
tube-shaped epithelial infoldings, known as crypts. All intestinal epithelial cell production
