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Mesenchymal stem cells for tissue engineering and regenerative medicine

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2006 Biomed. Mater. 1 63

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INSTITUTE OF PHYSICS PUBLISHING BIOMEDICAL MATERIALS
Biomed. Mater. 1 (2006) 63–71 doi:10.1088/1748-6041/1/2/003

Mesenchymal stem cells for tissue

engineering and regenerative medicine
Suk-Kee Tae, Seok-Hyn Lee, Jae-Sik Park and Gun-Il Im
Department of Orthopaedics, Dongguk University International Hospital, Goyang, Korea
E-mail: gunil@duih.org

Received 30 March 2006

Accepted for publication 6 April 2006
Published 26 April 2006
Online at stacks.iop.org/BMM/1/63

Abstract
Mesenchymal stem cells (MSCs) exist in bone marrow and other musculoskeletal tissues.
These cells contribute to the homeostasis of musculoskeletal tissue as well as support for the
growth and differentiation of primitive hemopoietic cells. Recent advancements in tissue
engineering and regenerative medicine have highlighted MSCs as a potential source of cells
which would differentiate to a variety of tissue tailored to individual needs. This paper briefly
outlines the current status of MSCs, focusing on their biological characteristics and potential
for clinical applications.

1. Introduction
Bone marrow contains mesenchymal stem cells (MSCs) which
support hematopoietic stem cells and provide progenitors
for several mesenchymal tissues, including bone, cartilage,
tendon, fat and muscle [1]. Comparable adult stem cells
have also been isolated from a wide variety of tissues. These
cells can differentiate into specialized cells with a phenotype
distinct from that of the precursor under the influence of
appropriate signals.
MSCs were first identified in the pioneering studies of
Friedenstein, who isolated bone-forming progenitor cells from
rat marrow [2]. MSCs represent a very small fraction, 0.001–
0.01%, of the total population of nucleated cells in marrow
[3]. However, they can be isolated and expanded with high
efficiency, and induced to differentiate to multiple lineages
under defined culture conditions. Along with their extensive
capacity for self-renewal, stem cells display a broad potential
for generating diverse differentiated progenies.
Adult stem cells had been considered to be
developmentally committed so that a kind of stem cell
generates specific cell lineages. This concept has been
radically challenged by several uncanny and unanticipated
discoveries. Recent studies have demonstrated that particular
stem cells, besides producing an expected set of cell
characteristics of the tissue they reside in, also give rise
to a set of totally different cells. MSCs can give rise to
nonmesenchymal cells such as neural cells or epithelial cells
as well as a variety of mesenchymal phenotypes such as bone,
cartilage, fat and muscle [4, 5]. In addition, to meet the
high demand for precursors during tissue growth and repair,
uncommitted progenitors can be recruited from other tissue
sources [6].
The multipotential of MSCs, their easy isolation and
culture, and their high ex vivo expansive potential make
these cells an attractive therapeutic tool for potential use in
regenerative medicine and tissue engineering.
2. In vitro characteristics of mesenchymal stem cells
Even though MSCs can be easily isolated and expanded in
culture through many generations while retaining the capacity
to differentiate, little information is currently available about
the biology of stem cells in vivo and their precise role in tissue
repair or regeneration. This may be due in part to the lack of
useful cell-specific markers. MSCs can differentiate in vitro
into cells of connective tissue lineages, including bone, fat,
and cartilage under appropriate culture conditions.
2.1. Isolation and characterization of MSCs
MSCs are generally isolated from bone marrow aspirates
harvested from the superior iliac crest of the pelvis in humans
[3, 7] although other sources such as the tibial and femoral
marrow compartments [8, 9] and the thoracic and lumbar
spine are also available [10]. Although they represent a
minor fraction of the total nucleated cell population in marrow,
MSCs can be plated and enriched using standard cell culture

1748-6041/06/020063+09$30.00 © 2006 IOP Publishing Ltd Printed in the UK 63

S-K Tae et al
Figure 1. Human mesenchymal stem cells from bone marrow
growing in vitro on the floor of a plastic dish.
techniques. The marrow sample is fractionated on a density
gradient solution. Then the cells are plated at densities ranging
from 1 × 104 cells cm−2 to 0.4 × 106 cells cm−2 [3, 11,
12]. Cells are generally cultured in a basal medium such as
Dulbecco’s modified Eagle’s medium (high glucose) in the
presence of 10% fetal bovine serum (FBS) [3]. MSCs have
a fibroblastic morphology in a monolayer culture and adhere
to the tissue culture substrate. Primary cultures are usually
maintained for 12–16 days, during which time the nonadherent
hematopoietic cells are removed with the exchange of the
medium. The addition of fibroblast growth factor-2 (FGF-2)
to primary cultures of human MSCs leads to an enhanced
proliferation and osteogenic potential [13]. Although plastic
adherence remains the principal method to isolate MSCs,
immunodepletion methods involving CD34/CD45/CD11b
may be used to generate purified MSC preparations [14].
By light or phase contrast microscopy, MSC cultures
display a rather homogenous population of fibroblast-like cells
(figure 1). While a small fraction of MSCs actively proliferate
(approximately 10% at S + G2 + M), the vast majority of
cells are standing at the G0/G1 phase of the cell cycle [15].
After multiple passages, MSCs show a large but exceedingly
erratic expansive potential. MSCs cannot be expanded over
30–40 doublings [16, 17]. This is determined by several
factors: the procedures for harvesting the marrow [16–18];
the frequency of MPC in marrow harvests (2–5 MPC per
1 × 106 mononuclear cells) [19]; the age or condition of the
donor [20]. After extensive subcultivation impairs, cells show
evident signs of senescence and apoptosis [15].
2.2. Surface markers of MSCs
In order to characterize MSCs, the antigenic phenotypes
of MSCs have been studied. The antigenic types are not
unique, and also vary with subcultures. It shows features
of mesenchymal, endothelial, epithelial and muscle cells.
In general, MSCs do not express the typical hematopoietic
antigens such as CD45, CD34 and CD14 [15, 21]. There are
several antibodies that were extensively investigated by several
groups. STRO-1 was identified as an antibody that reacted
64
Figure 2. Human mesenchymal stem cells from bone marrow are
strongly positive for STRO-1 antibody (left) and negative for CD-34
(right).
with non-hematopoietic progenitor bone marrow stromal cells
(figure 2) [22]. The SB-10 antibody was shown to be reactive
with an antigen present on undifferentiated MSCs, which
disappeared after the cells began the osteogenic differentiation
and express cell surface alkaline phosphatase [23]. The
specific SB-10 antigen was later identified as CD166 (activated
leukocyte-cell adhesion molecule, ALCAM) [23], which may
play a role in the progression of osteogenic differentiation.
The SH-2 antibody reacts with an epitope present on the
transforming growth factor-beta (TGF-β) receptor endoglin
(CD105) [21]. Both the SH-3 and SH-4 antibodies [24]
apparently recognize distinct epitopes on the membrane-bound
ecto-5-nucleotidase (CD73) [21]. SH-2, 3, 4 antibodies do
not react with hematopoietic cells or with osteocytes [24].
Regrettably, all of the antigens are also expressed on a host
of other cell types and do not provide the specificity needed
to extend these studies to in vivo evaluation of tissue-specific
stem cells.
MSCs express a large spectrum of cell adhesion molecules
that have potential importance in cell binding and homing
interactions. CD44, a receptor for various ligands such as
hyaluronan and osteopontin, is also expressed and particularly
[15] plays a central role in the organization of the extracellular
matrix in the marrow or in the bone [25, 26]. Expression of
specific integrins also plays a role in homing to sites of injury
and binding to specific matrix molecules [27].
2.3. Differentiation of MSCs
Osteogenic activation requires β-glycerol-phosphate, ascorbic
acid-2-phosphate, dexamethasone and fetal bovine serum.
When cultured in a monolayer in the presence of these
supplements, the cells acquire an osteoblastic morphology
with upregulation of the alkaline phosphatase activity and
deposition of a calcium-rich mineralized extracellular matrix.
Chondrogenic differentiation occurs when MSCs are
grown in a three-dimensional culture format, a serum-free
nutrient medium and the addition of a member of the TGF-
β super-family such as TGF-β1, β2, β3 or BMPs. When
these conditions are met the cells initiate an expression of a
number of cartilage-specific extracellular matrix components

and a spectacular change in cell morphology. TGF-
β1, β2 and β3 have the ability to induce this response
although TGF-β2 and 3 are more effective than β1 in
promoting chondrogenesis [28]. During differentiation in
the presence of TGF-β, MSCs synthesize all components of
the normal articular cartilage matrix (aggrecan, link protein,
fibromodulin, cartilage oligomeric matrix protein, decorin,
type II collagen) [28].
MSCs cultured in a monolayer in the presence of
isobutylmethylxanthine become adipocytes with large lipid-
filled vacuoles. Adipogenic differentiation of MSCs is induced
by the nuclear receptor and transcription factor, peroxisome
proliferator-activated receptor-gamma (PPAR-γ ). Both IL-1
and TNF-α suppress adipogenesis, which is mediated through
NF-κB activated by the TAK1/TAB1/NF-κB induction kinase
cascade [29]. The effect of inhibition by these cytokines
leads to differentiation toward osteogenesis. Induction of
myogenesis by 5-azacytidine was reported for embryonic and
adult cells [30, 31].
Treatment of MSCs with isobutylmethylxanthine and
dibutyryl cyclic AMP induced expression of early markers of
neuronal differentiation [32]. Transdifferentiation of mouse
marrow stromal-derived mature osteoblasts and the stromal
cells themselves to a neural phenotype was achieved by
treatment with 5-azacytidine in the presence of nerve growth
factor, BDNF and neurotrophin-3 [33]. Treatment of rat
cells with DMSO/butylated hydroxyanisole in the presence
of bFGF and PDGF was also successful in inducing a neural
phenotype [34].
3. Tissue-specific mesenchymal stem cells
In addition to marrow, other sources of stem cells with
mesenchymal potential include periosteum [35, 36], trabecular
bone [37, 38], adipose tissue [39–41], synovium [42], skeletal
muscle [31], lung [43] and deciduous teeth [44].
3.1. Muscle-derived MSC
Work performed with adult human skeletal muscle has
demonstrated the existence of cells with properties of early
myogenic progenitors [45]. A mixture of stellate-shaped
cells and multinucleated myotubes was formed after tissue
enzymatic dissociation and cell cultivation. Cells showed
signs of differentiation when dexamethasone was added
[46]. The differentiated population included cells with the
phenotype of skeletal and smooth muscle, bone, cartilage and
fat. In addition, there was a minor cellular subset that contains
slowly dividing cells in culture but rapidly after grafting
was preset. The subset probably represents uncommitted
mesenchymal stem cells that persist in the environment of
the recipient muscle. These cells [47–49] seem to be different
from muscle satellite cells that are considered as the muscle
stem cell [50].
Cells from myocardium also exhibit properties of
mesenchymal progenitors. It has been reported that
cultures of neonatal rat heart gives rise to a population
of adherent cells which generate several mesenchymal
Mesenchymal stem cells for tissue engineering and regenerative medicine
phenotypes with characteristics of adipocytes, osteoblasts,
chondrocytes, smooth muscle cells, skeletal myotubes and
cardiomyocytes when treated with dexamethasone [51]. It
has not been confirmed whether muscle- and bone marrow-
resident mesenchymal stem cells represent the same kind of
progenitor. However, the work by Ferrari et al [6] has provided
strong evidence that the populations of muscle progenitors
present in skeletal muscle are derived from uncommitted
bone marrow mesenchymal progenitors and are different from
muscle satellite cells.
3.2. Bone-derived MSC
Four cellular subsets were sorted from primary cultures of
human bone, depending on expression of the stromal precursor
cell marker STRO-1 and the osteoblastic marker alkaline
phosphatase (ALP) [52]. The STRO-1+/ALP-subset showed
a preosteoblastic phenotype with a reduced ability to form a
mineralized bone matrix and the lack of expression of bone
sialoprotein, osteopontin and parathyroid hormone receptor.
Only these subpopulation cells gave rise to all of the four
subsets of STRO-1/ALP cells present in the primary culture.
Thus, these results have demonstrated that cultures of human
bone yield osteoprogenitors as well as end-stage differentiated
osteoblasts.
Studies with nonimmortalized clonal cell lines derived
from human trabecular bone have shown that bipotent-
(osteo/adipo) committed progenitors are also present. Thus,
uncommitted mesenchymal stem cells are also ubiquitously
positioned in bones which, under appropriate stimuli, may self-
renew, commit and generate cells exhibiting the phenotypic
and functional characteristics of the bone or adipose
tissue [53].
3.3. Adipose tissue-derived MSC
Adipose tissue stromal cells contain adipocyte progenitors
at various stages of maturity, including the stromal-vascular
(SV) cells, considered as the less differentiated tissue-
resident adipocyte progenitor. Those cells proliferate and
differentiate into mature adipocytes during cold acclimation
[54] and after caloric excess [55]. SV cells are a class of
fat-resident-committed mesenchymal progenitors, exhibiting
at least a bipotent differentiation potential, since they can
differentiate into adipocytes or chondrocytes [56]. They can
be induced to differentiate into adipocytes by glucocorticoids
[57]. Stem cells from adipose tissue, variously referred
to as processed lipoaspirate (PLA) cells [40], have been
shown to have similar differentiation potentials [39]. There
is a little difference between cells from marrow and fat in
terms of yield, growth kinetics, cell senescence, multi-lineage
differentiation capacity and gene transduction efficiency. The
utility of these cells in therapeutic applications may then
depend on the availability of tissue specimens and the ease of
in vitro expansion. However, recent works on the osteogenic
and chondrogenic potentials of adipose-derived MSCs show
inferior capacity for osteogenesis or chondrogenesis compared
with bone marrow-derived MSCs [58, 59].
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S-K Tae et al
4. Mobilization of mesenchymal stem cells
Bone marrow stroma can feed progenitors into distant tissues
[1]. Thus, the mesenchymal stem cell must leave the marrow
stroma for destinations in other tissues. Cell-to-cell or cell-
to-matrix interactions between mesenchymal progenitors and
stromal components should loosen up in order to facilitate
the entrance of the progenitor into the blood stream. Then
peripheral blood should provide a trail route for mesenchymal
stem cells in the search of their final destinations where they
are supposed to home, expand and further differentiate.
In addition to adult bone marrow and other mesenchymal
tissues, umbilical cord blood is also a source of mesenchymal
progenitors [60]. These ‘in motion’ mesenchymal cells
display many common features with adult human bone
marrow-derived mesenchymal progenitors, such as adhesion
to plastic, morphology, expression of cell membrane and
cytoplasmic antigens, and a potential to differentiate into
osteo/chondrogenic and adipogenic phenotypes. Moreover,
the identification in cultures of mesenchymal cells from cord
blood of a subset (5–10%) of quiescent cells suggests that
an uncommitted mesenchymal progenitor circulates during
gestation. The inverse correlation between content of
mesenchymal progenitors in cord blood and gestational age,
a trend also observed for hematopoietic progenitors [61],
suggests that mesenchymal cells travel from fetal sites into
other tissues early during development [60].
5. Therapeutic applications of mesenchymal stem
cells in regenerative medicine
As adult stem cells have presented several promising features
for the development of new cell therapies, researchers have
pursued a broad range of investigations for their therapeutic
utilization. MSCs can be locally applied for regeneration or
infused systematically depending on the purpose.
5.1. Direct loading
Direct loading is best suited to a clinical strategy oriented to
augment local repair or regeneration of bone [62–64], cartilage
[65], tendon [66] and fat [67, 68]. Moreover, therapeutic
use of marrow-derived MSCs addresses a broad spectrum of
indications, including cardiovascular repair, treatment of lung
fibrosis and spinal cord injury.
Locally delivered bone marrow cells can generate de novo
myocardium, indicating that stem cell therapy can be useful in
treating coronary artery disease [69]. The practical utility of
this approach was tested in a study involving the delivery of
bone marrow cells into the infarct zone in patients following
myocardial infarction [70]. A dramatic improvement in global
heart function was achieved as a result of this treatment.
Another study showed that engraftment of bone marrow-
derived cardiomyocytes in the adult heart following bone
marrow transplantation demonstrated that MSCs are tolerated
in a xenogeneic environment while retaining their ability
to be recruited to the injured myocardium and undergo
differentiation to a cardiac phenotype [71].
66
MSCs have also been shown to engraft at high levels
in lung tissue following exposure to bleomycin offering
protection against bleomycin-induced lung injury, including
inflammation and collagen deposition.
These observations have broad implications in the area of
lung disease associated with environmental damage [14].
Stem cells with the ability to differentiate into neurons,
astrocytes and oligodendrocytes have been isolated from rat
spinal cord [72], and implantation of neural stem cells in an
adult rat model of spinal cord injury resulted in long-term
functional improvement [71]. The ability of bone marrow-
derived MSCs to differentiate into neural lineages in vitro
and after transplantation in both mice and rats provoked the
expectation that they may be useful in the treatment of stroke,
traumatic injury and Parkinson’s disease. Furthermore, it was
recently verified that adult human bone marrow cells could
enter the brain and generate neurons after transplantation [73].
In orthopedics, there are many applications involving
local delivery of MSCs, which include repair of focal defects
in articular cartilage [74, 75], tendon [76], ligament [77],
intervertebral disk [78], spine fusion [79], the repair of
segmental bone defects [80] and craniotomy defects [81]. In
an animal model of osteoarthritis, delivery of stem cells by
intraarticular injection resulted in engraftment of those cells
on the meniscus, fat pad and synovium with regeneration of
meniscal tissue and protection of the cartilage.
5.2. Systemic infusion
A selective homing follows the infusion of mesenchymal
progenitors from bone marrow into marrow stromal sites [82].
The homed MSCs facilitate engraftment and differentiation
of hematopoietic stem cells, which improves the function of
hematopoietic-supporting stroma [83, 84].
Although the issue of transplantation has been addressed
in several studies, results are rather contradictory in
establishing the origin (host or donor) of mesenchymal
progenitors after allogeneic transplantation of marrow harvests
[19, 20, 85–88]. In addition, it has been demonstrated that
stemness of the grafted cells determines repopulation of the
damaged tissue [89, 90]. It is not certain whether the same
occurs after transplantation of ex vivo expanded mesenchymal
progenitors since progenitor stemness and function diverge as
cells are subcultivated [15].
Systemic infusion of ex vivo expanded autologous
mesenchymal progenitors is feasible and safe in the short
term [82, 91]. On the other hand, the low immunogenic
nature of MSCs allows broad application in terms of allogeneic
therapy. There are several reports describing the clinical use
of allogeneic donor-mismatched cells with little evidence of
host immune rejection or GVHD. Allogeneic bone marrow
transplantation in children with osteogenesis imperfecta
results in impressive histological changes in trabecular bone,
which are indicative of new dense bone formation [92].
Engraftment of allogeneic MSCs has also been demonstrated
in a patient with severe idiopathic aplastic anemia with
improvement of marrow stromal function [93].

6. Application of mesenchymal stem cells for
cartilage tissue engineering
Damage to cartilage is of great clinical consequence because
it has a poor regenerative capacity and its replacement tissue,
fibrocartilage, is mechanically inferior to normal hyaline.
Due to the lack of blood supply, the subsequent wound
healing response and the lack of the intrinsic ability of native
chondrocytes to participate in regeneration at the injury site
damage to cartilage results in incomplete repair.
The current treatment options (e.g., surgical intervention)
to repair damaged articular cartilage are less than satisfactory,
and rarely restore full function or return the damaged tissue to
its normal biologic state.
The final treatment for articular cartilage reconstruction
is joint replacement arthroplasty [94, 95]. Although total
joint replacement has advanced during the last 40 years, it
is still fraught with a number of drawbacks such as infection,
loosening and periprosthetic osteolysis.
On the other hand, the low degree of vascularization
in cartilage makes it an ideal target for tissue engineering.
Tissue engineering combines the principles of engineering
and biology to design and fabricate constructs to expedite the
repair and regeneration of damaged tissue. The underlying
principle of tissue engineering involves the utilization of
biocompatible and mechanically suitable scaffolds, combined
with an appropriate source of cells and bioactive molecules to
promote the differentiation and maturation of the cell type
of interest. These components, when combined, form a
tissue-engineered construct, which can function as the tissue
replacement material and, in principle, facilitate a faster rate
of tissue repair. Tissue engineering may offer great promise
for the regeneration of cartilage.
One of the great challenges facing cartilage tissue
engineering is designing constructs that mimic the unique
multiphasic cellular architecture and mechanical properties of
native cartilage tissue. As such, successful cell-based cartilage
tissue engineering will depend on not only the selection of
an appropriate biocompatible scaffolding material, but also
materials with suitable mechanical properties that will result
in a desirable clinical outcome when combined with cells and
bioactive molecules.
6.1. Cells for cartilage tissue engineering
Selecting an ideal source of cells for cartilage tissue
engineering requires the achievement of a number of criteria,
which include easy access and availability of the source cells,
an extensive self-renewal or expansion capability of the source
cells, a capacity to differentiate readily into cell lineages of
interest upon instructive signal, and a lack of or minimal
immunogenic or tumorigenic ability of the source cells.
Over the years, three major cell types have been examined
for their potential application in cartilage repair and tissue
engineering, namely committed chondrocytes, embryonic
stem (ES) cells and adult stem cells. Each of these cell
types has demonstrated its limitations and advantages over
the others due to their intrinsic biological properties, such as
their proliferative and differentiation potentials, availability
Mesenchymal stem cells for tissue engineering and regenerative medicine
of large quantity of cells for transplantation and ethical and
legal concerns. For example, committed chondrocytes isolated
from hyaline cartilage by enzymatic digestion have been
tested extensively as a cell source to be injected into the
damaged articular cartilage site for repair. However, their wide
usage in clinical trials and tissue engineering applications has
been held up because of the loss of redifferentiation capability
after relatively limited in vitro expansion. In contrast, ES cells
derived from the inner cell mass of the embryonic blastocyst
have infinite proliferation potential and are able to generate
cell characteristics of all three germ layers under appropriate
inductive conditions. However, the ethical and legal concerns
associated with ES cells and their tumorigenic potential make
them a less ideal cell source in basic research and clinical
applications. On the other hand, adult stem cells (e.g., MSC)
derived from various tissues (e.g., BM, fat and trabecular
bone) demonstrate a promising future in regenerative medicine
because of their ability of self-renewal and differentiation
along specific lineages upon stimulation.
6.2. Scaffolds for cartilage tissue engineering
In addition to selecting an appropriate source of cells for
cartilage tissue engineering, the design of an engineered
cartilage construct, i.e. the scaffolding material in which
the cells will reside, needs careful consideration. The
physical properties (e.g., architecture, macro/microporosity,
interconnecting porosity and topography) of an engineered
tissue substitute will play an integral role in altering its
biological performance. Therefore, an ideal tissue engineering
scaffold should possess a number of key properties, including
being biocompatible, biodegradable, porous, mechanically
stable, cell permissive and conducive to extracellular
matrix production and deposition and biomolecular signal
transmission. Natural materials used to produce a bioactive
scaffold for stem-cell-derived cartilage include agarose,
alginate, hyaluronic acid, gelatin, fibrin glue and collagen
derivatives. The principal disadvantage of these constructs is
their mechanical fragility, which severely restricts their clinical
usefulness. The mechanical and biochemical qualities and the
degradation of synthetic biomaterials are more easily modified
than those of natural polymers. They can be fabricated as
needed and can be manufactured with more uniform properties
and purity. Polyglycolic acid is a long-standing, well-studied
scaffold for engineering neocartilage, but degrades at a faster
rate and is weaker than most synthetic scaffolds [96, 97]. The
polylactides are slow absorbing polymers. Polylactic acid
press-coated with human MSCs has been shown to support
chondrogenesis in vitro [98, 99]. Poly(lactic-co-glycolic acid)
and poly(ethylene glycol) blended into a polymeric foam of
ratio 80/20, polydioxanone, and the copolymer poly(L-lactide-
E-caprolactone) prepared as a nanofibrous scaffold are also
reported to be useful scaffolds for the chondrogenic induction
of human MSCs (figure 3) [100].
Hydrogels are developed with a view to being customized
for small, complex geometrical defects typically exhibited
in facial structures. These can fill tissue defects using
minimally invasive procedures and be molded to the specific
67
S-K Tae et al
Figure 3. Repair of an osteochondral defect with the implantation
of the composite of MSCs and polydioxanone scaffold in the rabbit
(left), control without implantation (right). Safranin-O staining
(×40).
shape. Photopolymerizing poly(ethylene glycol)-diacrylate
is a recently investigated system for engineering osteogenic
and chondrogenic cells from MSCs [101–103]. A variety of
hybrid scaffolds using both synthetic and natural polymers can
be used for the effective delivery of MSCs. They combine the
better biocompatibility of natural polymers with the strength
and moldable nature of synthetic polymers. Problems with
purity, isolation and supply of the natural component remain
a concern.
7. Conclusion
Recent enthusiasm for stem cells has contributed to the
current knowledge in the biology and clinical application of
MSCs. However, this information is not yet sufficient for
establishing MSCs as safe and effective therapeutic tools for
tissue regeneration. Although much has been learnt about
MSCs in the past few years, much more remains to be
discovered in the future. A multidisciplinary approach would
be necessary for the best effort to accomplish the goal of
using MSCs as the universal ‘stuff’ in tissue engineering and
regenerative medicine.
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