Biomedical Engineering Reference
In-Depth Information
1.
Stem Cells and the Art of
Mesenchymal Maintenance
Kevin C. Hicok and Marc H. Hedrick
1.1 Introduction
these cells to determine similarity to hES cells
generated via sexual reproduction has not yet
advanced far. Furthermore, teratoma forma-
tion by hES cells remains a safety issue, so that
large-scale clinical trials involving these cells
cannot be undertaken until the safety issue is
resolved.
Adults also have stem cells. Hematopoietic
stem cells in the bone marrow that can recon-
stitute the immune system have been known
and studied for many years [
The most promising emergent medical tech-
nology of the early twenty-fi rst century is
stem-cell therapeutics. Traditionally, stem cells
possess two important characteristics: the
ability to undergo nearly unlimited self-renewal
and the capability to differentiate into many
(multipotent/pluripotent) or all (totipotent)
mature cell phenotypes. The existence of stem
cells and their ability to generate every tissue
of the body during embryonic development
has been known for many years. Transplant
experiments performed in the
]. Stem cells in
the liver allow rapid regeneration after liver
surgery; stem cells in the dermis undergo con-
tinuous cell division and differentiation to
replace skin cells; and mesenchymal stem cells
(MSCs) in bone provide osteoblasts for bone
remodeling throughout life. Until the mid-
1980
13
s, in which
single stem cells were injected into early-stage
blastulas, produced a chimera of donor and
recipient cells in each organ of the resultant
animal [
1970
s, these stem cells were thought to be com-
mitted to regenerating only the tissue in which
they resided and were believed to be unable to
differentiate toward cell fates not associated
with their germinal layer of origin. Their poten-
tial as “true” stem cells was therefore not real-
ized. In the
].
The isolation and propagation of human
embryonic stem cells (hES), however, has
been achieved only relatively recently [
29
,
47
].
Political, moral, and ethical concerns sur-
rounding procurement of these cells from
embryos have held back their development as a
source of cells for therapeutics or tissue engi-
neering. Research efforts in the fi eld of thera-
peutic cell cloning have skirted these issues by
providing alternative methods, such as somatic
cell nuclear transfer (SCNT), that generate
hES cells without the use of intact embryos
[
111
s, the molecular mechanisms
involved in cellular differentiation began to be
understood more fully. Moreover, development
of in vitro differentiation assays helped cell
biologists and tissue engineers realize the ther-
apeutic potential of these cells. This chapter
will review the successes, challenges, and future
prospects of using stem cells in the tissue
engineering of bone, cartilage, tendon, and
ligament.
1990
]. Until recently, the success rate of SCNT
was extremely low, and the characterization of
46
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