Biomedical Engineering Reference
In-Depth Information
Therefore, MSCs are expected to be an ideal source for transplantation or liver tissue
engineering: however, the hepatic differentiation of MSCs is still insufficient for clinical
application. But the proliferation and the differentiation capacity of ASCs also cause
changes in their metabolic activity. These changes may, in turn, increase the risk of tumor
formation [42].
Neural Stem Cells
Neural stem cells (NSCs) differentiate into three major cell types: neurons, astrocytes, and oli-
godendrocytes [43]. The NSCs that have been identified in the ventricular zone of the brain
include neuroblasts, precursor cells and astrocytes. They all express proteins like GFAP (glial
fibrillary acidic protein) and the glycoprotein CD133, which permits the identification of this
cell. Most NSCs of the lateral ventricles (ependymal cells) are quiescent and do not perform
active division. The NSCs express nestin, which is a specific marker of neural precursors.
Furthermore, NSCs of the hippocampus are ciliated and play an important role in the memory
function of the brain. They express neuronal markers, such as NeuN, neuron specific enolase,
and calbindin [44].
Neural stem cells are commonly cultured
in vitro
as so-called neurophases. In this case,
they assume a free-floating cell cluster configuration. By using the neurophase in cell culture,
NSCs are capable of differentiating into glial-like cells [45]. It is believed that they have the
potential of curing brain disorders, such as anxiety, depression, memory deterioration, and
some brain tumors [8]. Furthermore, there is some speculation that these cells may overcome
the paralyzation caused by spinal cord injuries [46, 47].
Neural Crest Stem Cells
A remnant of embryonic neural-crest stem cells has been identified in the hair follicles. Similar
cells have also been found in the gastrointestinal tract, in the sciatic nerve, and in the spinal
cord. Neural crest stem cells can differentiate into neurons, Schwann cells, myofibroblasts,
chondrocytes, and melanocytes [48].
Hematopoietic Stem Cells
Nearly 50 years ago, HSCs were identified by Till and McCullough [49]. The remarkable
characteristics of these cells are their ability for continuous self-renewal in the bone marrow
and their ability to differentiate to all types of blood cells (Figure 1.1). Hematopoietic stem
cells normally reside in bone marrow, but under certain conditions they migrate through the
blood in order to settle in other tissues. They are also present in fetal liver, the spleen, placenta
blood, and in the umbilical cord. A decade ago, several studies have revealed that HSCs can
give rise to a liver-like cell phenotype [23, 50]. One study has demonstrated that HSCs that
are transplanted into an irradiated mouse evolve not only into various blood-cell types (from
the mesoderm layer of the embryo), but also into epithelial cell phenotypes in the lung, gut
(endoderm layer), and skin (ectoderm layer) [51]. If HSCs are truly multipotent, their poten-
tial for life-saving regenerative therapies may be considerably expanded in the future.
There are several problems concerning the implementation of standardized HSC protocols.
The identification and characterization of HSCs is difficult, as those with long-term repli-
cating ability are rare and difficult to upscale. Furthermore, HSCs have multiple phenotypes
and resemble other blood or bone-marrow cells, which makes them difficult to distinguish
from each other [52].
