ENGINEERING PEPTIDES IN HYDROGELS FOR CARTILAGE TISSUE REGENERATION - Biologically-Responsive Hybrid Biomaterials - page 309

[154-156] since cartilage is an avascular tissue. MSCs can be isolated from bone
marrow, adipose tissue and many other adult tissues [157]. Normally, MSCs are
characterized by their capacity to adhere to plastic, their phenotype (CD73 + ,
CD90 + , CD105 + , CD14 - or CD11b - , CD19 - or CD79a - , CD45 - and HLA - DR - ;
with CD34 being expressed solely by adipose-derived MSCs) and their potential
to differentiate into adipocytes, chondrocytes and osteoblasts [158] even though
comprehensive protocols to confirm their identities are not available yet. It is still
not clear whether MSCs from different tissues are the same population of cells
[152]. Both bone-marrow-derived and adipose-derived MSCs have been mostly
studied due to their ease in isolation [11, 159]. However, tissue source, donor
age, and disease stage can directly affect MSC yield, rate of proliferation and
multipotency. In a comparative study of MSCs isolated from 5 different tissue
sources, synovium-derived stem cells were shown to have the greatest
chondrogenic potential [160]. One exciting finding is that the zonal organization
of chondrocytes in articular cartilage tissue might be able to be recapitulated
by MSCs [161, 162]. Recently, MSCs have also been described as
immunoregulatory cells and thus hold great potential for allogeneic use in
treating arthritic diseases as well [163]. Murphy et al found that MSCs could
delay cartilage destruction in a traumatic injury model by a direct intra-articular
injection of MSCs [164]. This suggests different mechanisms of cartilage tissue
engineering between ex vivo engineering and direct in vivo delivery. Therefore,
MSCs are clearly not just considered as a cell source of chondrocytes, but also as
a vehicle of many biofactors for inducing tissue regeneration.
It has been established that biofactors TGF- Ȳ superfamily members including
TGF- Ȳ 1, TGF- Ȳ 2, TGF- Ȳ 3 and BMPs, as well as insulin-like growth factors, Wnt
proteins and fibroblast growth factors (FGFs) are essential for in vitro
chondrogenic differentiation of MSCs [163]. Extensive studies [163] have
been performed for in vitro chondrogenic differentiation of MSCs with the
optimization of biomaterials, biofactors, mechanical stimulations (fluid flow,
shear stress, intermittent hydrostatic pressure, and dynamic deformation loading).
At current stage, most of in vivo studies for cartilage repair using MSCs have
combined the delivery of biofactors via either directly encapsulated in scaffolds
or incorporated into microspheres for better controlled release [165-167]. Studies
[91, 95] comparing the biochemical and mechanical properties of tissue
constructs engineered by MSCs and chondrocytes clearly suggested that further
optimization is needed before MSCs exclusively can be used for functional
cartilage tissue engineering. In a clinical trial on human OA patients, autologous
bone-marrow MSCs embedded in collagen gel were transplanted into the