Biomedical Engineering Reference
In-Depth Information
cell fraction of the bone marrow. Bone marrow-derived MSCs pose advantage in
regenerative medicine because they are naturally poised to generate a particular
tissue, which might consist of several cell types such as adipocytes, chondrocytes,
osteoblasts, tenocytes, myoblasts, and neurocytes.
31
MSCs express CD44, CD73,
CD90, and CD105 receptors while lacking hematopoietic stem cell markers such as
CD34 and CD45. MSCs exhibit low expression of major histocompatibility complex
(MHC) class I and are negative for MHC class II antigens.
32
Various studies have
shown that in vitro expanded MSC preferentially home to sites of tissue damage,
where they enhance wound healing, support tissue regeneration, and restore the bone
marrow microenvironment.
33
However, the exact signaling events that drive MSCs
toward this repair mechanism are unknown. MSCs have been applied as therapeutic
agents for tissue repair owing to their immunomodulatory properties.
34
All of these
properties of MSCs make them an ideal cell source for tissue engineering.
35
2.3.2 Embryonic Stem Cells
ESCs are isolated from the inner mass of blastocyst cells.
36
Under defined condi-
tions, ESCs are capable of propagating themselves indefinitely. This allows ESCs to
be employed as useful tools for both research and regenerative medicine, because
they can produce limitless numbers of themselves for continued research or clinical
use.
37
Human ESCs are known to express antigens such as octamer binding protein
(Oct-4), Nanog, alkaline phosphatase, LIN28, rex-1, crypto/TDGF1, SOX2, and
stage-specific embryonic antigen (SSEA) 3 and 4. They also show high levels of
telomerase activities.
38,39
It is understood that Oct-3/4 along with SOX2 and Nanog
play a crucial role in the process of self-renewal,
40
whereas genes such as Klf4 and
c-Myc are involved with maintenance of pluripotency.
41
Because of their plasticity
and potentially unlimited capacity for self-renewal, ESC therapies have been
proposed for regenerative medicine and tissue replacement after injury or disease.
Diseases that could potentially be treated by pluripotent stem cells include a number
of blood- and immune system-related genetic diseases, cancers, and disorders;
juvenile diabetes; Parkinson's disease; blindness; and spinal cord injuries. Besides
the ethical concerns of stem cell therapy, ESCs face certain major technical
challenges such as histocompatibility and graft-versus-host disease.
2.3.3 Induced Pluripotent Stem Cells
A few years ago, a completely new class of stem cells was introduced by Takahashi
and Yamanaka.
42
The group demonstrated that uptake of genes such as Oct-3/4,
Sox2, c-Myc, and Klf4 induces pluripotent properties in somatic cells. These
reprogrammed cells were termed iPS cells.
42
Currently, many researchers are
actively studying the generation of iPS cells from various sources and trying to
improve the experimental procedures.
43
iPS cells are similar to natural pluripotent
stem cells, such as ESCs, in many respects, including the expression of certain stem
cell genes and proteins, chromatin methylation patterns, doubling time, embryoid
body formation, teratoma formation, viable chimera formation, and potency and
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