Biomedical Engineering Reference
In-Depth Information
2004). In either case, more evidence is needed to identify the location of stem cells
in the adult brain.
The way scientists think of the CNS and CNS therapies continues to change,
as evidence accumulates for the use of NPCs in CNS injury. Studies are indicating
that the CNS has greater self-repair potential than was once believed, in part due
to investigations into NPC behavior. For example, degeneration of motor neurons
seems to trigger a response in NPC proliferation, migration and neurogenesis in
the lumbar region of the adult spinal cord (Chi et al. 2006).
The SVZ and SGZ, as well as other areas with NPC activity, serve as models
for the study of neurogenesis
in vivo
because of migration, differentiation, and
maturation of NPCs. These areas are interesting because the mature daughter
progenitor cells that arise from asymmetric cell divisions
2
, in both the SVZ and
dentate gyrus of the hippocampus, migrate to distinct targeted areas as they
mature. At the targets, the progenitor cells may completely differentiate or
become quiescent (Watts et al. 2005). Cellular signaling occurs throughout this
process. Thus, within these niches lie guidance, fate-specifi c, and proliferative cues
that control NPC behavior. Suspected cues are being studied to discern the
complex task of controlling NPCs.
Cues or signals can be proteins that make up the extracellular matrix or pro-
teins that come from surrounding cells, such as secreted soluble proteins and
membrane-bound proteins that come in contact with progenitor cells. Proteins
used for interaction or communication between NPCs and astrocytes, oligoden-
drocytes or neurons are of interest because these CNS cells are involved in every
phase of neurogenesis in the adult brain. Astrocytic cues are of particular interest
because astrocytes are the most abundant cell type in the brain and are found in
neurogenic niches.
18.3.3 NPC Fate Identifi cation
To determine the fate of differentiated NPCs and to distinguish other cell types
when co-cultured with NPCs, immunocytochemistry and fl uorescence micros-
copy are used. Most often NPCs are derived from transgenic (genetically modi-
fi ed) mice that express green fl uorescent protein (GFP). The GFP in NPCs is
ubiquitous, making NPCs easily distinguished from other cells when co-cultured
with non-GFP cells using a fl uorescent microscope.
In ICC, antibodies with specifi c antigenic targets are used to identify proteins
that are unique to certain cell types. These antibodies are tagged with fl uorescent
probes that when exposed to a specifi c excitation wavelength(s) emit light allow-
ing the probes to be visualized. So if the cell is fl uorescent, it contains the cell-
type - specifi c protein identifi ed by the antibody. This does not conclusively prove
that the cells identifi ed are of a specifi c type, unless their functionality is tested.
2. Asymmetric cell division refers to daughter cells that differ in fate produced from the same cell.
For example, a stem cell can asymmetrically divide to produce one daughter cell like itself, able to
continue as a stem cell, and one daughter unlike itself, able to differentiate.
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