Volume 3 • Issue 3 • 1000e112
J Tissue Sci Eng
ISSN:2157-7552 JTSE an open access journal
Editorial Open Access
Pei, J Tissue Sci Eng 2012, 3:3
DOI: 10.4172/2157-7552.1000e112
Recent reviews of consecutive knee arthroscopies have
demonstrated the occurrence of chondral defects ranging from 60% to
65%, irrespective of the surgical indication [1]. Osteoarthritis, trauma,
and disorders of the subchondral bone – such as osteochondritis
dissecans or osteonecrosis, which secondarily afect articular cartilage
– may cause defects in cartilage. Based on current trends, osteoarthritis
is predicted to be the fourth leading cause of disability worldwide by
the year 2020 [2]. Articular cartilage is a unique, hypocellular, avascular
tissue mostly made of extracellular collagens and proteoglycans; it has
a limited ability to self heal afer trauma and degenerative disease [3].
Current clinical practice usually involves a bone marrow stimulation
technique in which subchondral bone is broken to facilitate cartilage
repair from bone marrow stromal cells (BMSCs) and cytokines.
However, with this procedure, cartilage defects are most ofen
repaired with fbrocartilage, which is known to be biochemically and
biomechanically diferent from native hyaline cartilage; this tissue
subsequently undergoes degeneration [4]. Autologous chondrocyte
transplantation (ACT) is currently used clinically; however, it has not
proven to be as successful as originally predicted [5]. Obtaining vital
and diferentiated chondrocytes presents one of the major challenges
for successful ACT. Each biopsy presents an additional trauma to
already damaged joint cartilage and may cause postoperative pain
and increase the long-term risk of developing osteoarthritis [4].
Furthermore, the expansion phase the chondrocytes have to undergo
in vitro leads to rapid cell de-diferentiation with a loss of chondrogenic
potential [6]. Additionally, isolation of cells from the cartilage matrix
by enzymatic digestion diminishes cartilage-specifc mRNA levels and
changes are exaggerated during expansion [7]. Te ex vivo expansion
of articular chondrocytes leads to a telomere erosion comparable to
30 years of aging in vivo [8]. Although re-diferentiation of these cells
has been shown in vitro [9], only partial gene expression was restored
[7] and a progressive loss of cell ability to form stable ectopic cartilage
in vivo became evident [10]. Tus, newly synthesized cartilage ofen
consists of more fbrous tissue than hyaline cartilage [11].
It becomes important to fnd an alternative, easily obtainable cell
source with stable chondrogenic potential [12]. Mesenchymal stem
cells (MSCs) are a promising cell source for cartilage regeneration
because, compared to articular chondrocytes, they are easily obtainable
in high numbers, expand in vitro without losing their diferentiation
potential [13], and have more pronounced expansion ability with
no higher risk for replicative aging [14]. Due to an ‘age phenotype’
of chondrocytes but not MSCs from patients of advanced age,
MSCs were found to be more attractive for cartilage repair in older
individuals. One possible source of MSCs is adipose tissue, which is
easily accessible in large quantities. Apart from a similar osteogenic
and adipogenic diferentiation potential, however, adipose-derived
MSCs showed a reduced chondrogenic diferentiation capacity under
standard induction conditions [15]. In addition to adipose tissue,
bone marrow is a particularly attractive source for MSCs. Some
recent reports indicated that BMSC-based repairs perform better
than chondrocyte-based ones [16,17], despite one report suggesting
that BMSC transplantation showed comparable results with ACT in
the repair of articular cartilage defects [18]. Compared to the ACT
approach having a greater efect in younger patients, transplantation
with BMSCs did not show any diference in ages older or younger than
45 [18]. A major hurdle in cartilage tissue engineering with BMSCs is
their diferentiation toward endochondral ossifcation [19]. During in
vitro chondrogenesis, BMSCs up-regulate not only hyaline cartilage-
specifc markers such as collagen II and aggrecan, but also markers
typical for hypertrophic chondrocytes such as collagen X and alkaline
phosphatase (ALP) [20-22]. Collagen X makes up 45% of the collagen
produced in hypertrophic chondrocytes and is therefore considered an
important marker of enchondral ossifcation [23]. In contrast, collagen
X is almost negligible in healthy mature chondrocytes and engineered
cartilage [24,25].
One of the challenges that need to be solved for the advancement of
regenerative cartilage medicine is to fnd a tissue-specifc stem cell that
generates articular cartilage-like chondrocytes and does not undergo
hypertrophy as a terminal diferentiation stage. Under chondrogenic
induction, BMSCs showed a 5- to 10-fold increase in osteocalcin
and ALP compared to synovium-derived stem cells (SDSCs) [26]; in
contrast, SDSCs have fewer tendencies to become hypertrophic when
incubated in a chondrogenic induction medium [27-33]. Figure 1
shows the diferent lineage tendencies of both human stem cells. Tere
is increasing evidence demonstrating that SDSCs are a tissue-specifc
stem cell for chondrogenesis [34]. Synovium is the closest tissue to
articular cartilage, not only in development but also in function; synovial
cells share properties with chondrocytes, such as cartilage oligomeric
matrix, link protein, and sulfated glycosaminoglycans (GAGs).
Synovium is also the only tissue that can produce hyaline cartilage in
benign conditions; under appropriate stimulatory conditions, synovial
cells are able to migrate into articular cartilage defects and subsequently
undergo chondrogenic diferentiation. It was demonstrated that
SDSCs match more closely with articular chondrocytes in gene profle
than BMSCs and are better at chondrogenic diferentiation than stem
cells from bone marrow, periosteum, adipose tissue, and muscle. Both
chondrocytes and synovial cells bordering the joint cavity could also
synthesize superfcial zone protein (SZP) that provides a protective
microenvironment for cartilage progenitor cells at the surface of
articular cartilage.
*Corresponding author: Ming Pei, Stem Cell and Tissue Engineering Laboratory,
Department of Orthopaedics, Exercise Physiology, and Mechanical and Aerospace
Engineering, West Virginia University, One Medical Center Drive, Morgantown,
PO Box 9196, WV 26506, USA, Tel: 304-293-1072; Fax: 304-293-7070; E-mail:
mpei@hsc.wvu.edu
Received September 04, 2012; Accepted September 05, 2012; Published
September 07, 2012
Citation: Pei M (2012) Can Synovium-derived Stem Cells Deposit Matrix
with Chondrogenic Lineage-specifc Determinants? J Tissue Sci Eng 3:e112.
doi:10.4172/2157-7552.1000e112
Copyright: © 2012 Pei M. This is an open-access article distributed under the
terms of the Creative Commons Attribution License, which permits unrestricted
use, distribution, and reproduction in any medium, provided the original author and
source are credited.
Can Synovium-derived Stem Cells Deposit Matrix with Chondrogenic
Lineage-specific Determinants?
Ming Pei*
Stem Cell and Tissue Engineering Laboratory, Department of Orthopaedics, Exercise Physiology, and Mechanical and Aerospace Engineering, West Virginia University,
Morgantown, WV 26506, USA
Journal of
Tissue Science & Engineering
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ISSN: 2157-7552