Biomedical Engineering Reference
In-Depth Information
developed leukemia whereas those injected with larger numbers of more mature
cells (CD34
+
CD38
+
) did not. The leukemia formed in immunocompromised
mice resembled the original patient disease in both cellular morphology and
their ability to home to the bone marrow. Further studies showed that AML
had a hierarchical organization that was similar to normal hematopoietic
development (Hope et al. 2004; Bonnet and Dick 1997). Taken together, this
was the first series of studies to identify and characterize a CSC. In addition,
these experiments also suggested the normal hematopoietic stem cells were
targets of transformation into leukemic stem cells. However, later studies
began to show some leukemic CSCs in patients were more similar to early
progenitors rather than a true hematopoietic stem cell (Tavil et al. 2006).
1.4 Properties of Normal Stem Cells vs. Cancer Stem Cells
A normal stem cell (SC) is defined by its ability to continually repopulate the
cells that comprise the organ system. Three properties that enable a stem cell to
do this are its differentiation capability (pluripotency), the ability to self-renew,
and a high proliferative capacity (reviewed in Tang et al. 2007). The ability of a
normal SC to support and propagate an organ or tissue must be tightly
regulated. A CSC requires these same properties to sustain and spread a
tumor. However, a CSC would not be subject to the same type of genetic
regulation as a normal SC (reviewed in Clarke 2005). It is also noteworthy
that the term ''cancer stem cell'' does not necessarily imply its origins are from a
SC, as there is the possibility CSCs emerge from early, less-differentiated cells or
mature, committed populations.
Pluripotency is the ability of a SC to differentiate into the heterogeneous
population of cells that comprise a tissue or, in the case of CSCs, a tumor (reviewed
in Lobo et al. 2007). A SC will give rise to a number of different cell types that can
be broken down into three groups: fully differentiated cells, transit-amplifying
cells, and stem cells (reviewed in Stingl and Caldas 2007). The fully differentiated
cells are mitotically inactive cells. They are at the end-stages of cellular differentia-
tion and will never re-enter the active cell cycle phase. The transit-amplifying (TA)
cells are fast growing cells that are not fully differentiated. TA cells are able to
proliferate for several generations but they eventually terminally differentiate and
need to be replenished by the SC (reviewed in Sell 2006). In order to maintain a
tissue or tumor a SC must be able to maintain its numbers by giving rise to
another, equally pluripotent SC. This property of SC is termed self-renewal.
Self-renewal is the ability of a SC to undergo asymmetrical or symmetrical
division (reviewed in Huntly and Gilliland 2005). Asymmetric division forms one
daughter and one SC, a mechanism of division is particularly useful to a SC
because it generates a TA cell while maintaining its self-renewing capacity.
Symmetrical division allows the SC to form two differentiated daughter cells or
two SCs. This behavior is critical because it allows the SC to expand its numbers.
