Biomedical Engineering Reference
In-Depth Information
made from a human condyle, photopolymer-
ized, and then transplanted subcutaneously
into immunocompromised mice. After
and viscoelastic, tribological, and anisotropic
properties must be assessed to determine
whether the new tissue can withstand in vivo
stress loads. Secondly, appropriate studies are
needed to establish the number of cells needed
per scaffold for the formation of adequate
amounts of cartilage, while avoiding necrosis
or apoptosis. If too many cells are implanted
into a wound, tear, or defect, the implant will
not be sustained because of insuffi cient
amounts of nutrients in the surrounding avas-
cular, acellular matrix.
Stem cells from different body sites should
be evaluated systematically for their chondro-
genic potential [
weeks,
the resultant construct retained both the shape
and the dimensions of the condyle and con-
tained osteoid and cartilaginous matrix. More
complex scaffolds can take advantage of stem-
cell multipotentiality and may better stimulate
the host environment, thereby providing appro-
priate niches for both bone and cartilage
repair.
Spinal disc repair represents another fi eld for
the use of stem cells in cartilage tissue engi-
neering. Cultures of ADSCs that also contain
nucleus pulposus cells give rise to type II col-
lagen and to aggrecan that is typical of nucleus
pulposus cells [
4
]. The evaluation should take
into consideration the relative ease of obtain-
ing the stem cells, donor site morbidity, and the
requirements for ex vivo expansion, as well as
the quantitative and qualitative differences in
the effi cacy of the engineered tissue generated
by the cells. Recent attempts to address these
issues include reports [
48
]. In conventional spheroid
cultures, adult MSCs express genes typical of
intervertebral disc nucleus pulposus cells,
including type II collagen, aggrecan, decorin,
fi bromodulin, and cartilage oligomeric matrix
protein, with the levels of expression typical of
disc cells rather than of hyaline articular car-
tilage [
68
] that stem cells
derived from synovium produced more carti-
lage than BM-MSCs, periosteal progenitors,
skeletal muscle, and ADSCs from the same
donor.
The therapeutic potential of cartilage syn-
thesized by stem cells is illustrated by a report
of two cases in which human BM-MSCs were
successfully used to treat patellar articular car-
tilage defects, with the two individuals report-
ing that they had less joint pain after
102
,
103
]. In contrast, chondrogenically
induced stem cells express type X collagen, an
indicator of chondrocyte hypertrophy and
eventual ossifi cation [
109
]. Ossifi cation in artic-
ular cartilage repair is necessary for tissue
integration with the surrounding bone tissue,
but in disc regeneration, ossifi cation of the
tissue is undesirable. However, if the surface
properties of the substrates on which the stem
cells are grown are altered, type X collagen
gene expression in BM-MSCs can be inhibited
[
83
1
and
2
years of follow-up [
]. Arthroscopy of the
injured sites showed that they contained fi bro-
cartilage [
118
]. Whether this also induces the expression
of the desirable proteoglycan proteins remains
to be determined.
A number of other stem-cell-dependent
variables are likely to infl uence the effi cacy of
the stem cell/scaffold constructs, and studies to
identify these variables are therefore war-
ranted. For example, the site from which stem
cells are harvested may infl uence their chon-
drogenic potential. Adult stem cells derived
from bone marrow and those derived from
adipose tissue appear to differ in their ability
to form cartilage in vitro [
83
118
].
1.7 Keeping Things Together:
Stem-Cell-Engineered
Ligament and Tendon
The use of stem cells to generate tissue-engi-
neered ligament and tendon holds great
promise. The cost of ligament repair alone
exceeded fi ve billion dollars in
]. The reasons
for these differences and whether the observed
differences are relevant in vivo remain to be
determined but may be important in planning
future therapies.
As yet, the mechanical properties of stem-
cell-derived cartilage have not been character-
ized for most model systems. Tissue strength
42
,
48
]. The
current “gold standard” for repairing the most
commonly injured ligament, the anterior cruci-
ate ligament, is by implantation of autografts
that consist of either patellar tendon or two
hamstring tendons that are harvested at the
time of surgery [
2002
[
89
]. The rates of failure and
recurrence of anterior cruciate ligament injury
115
