CELL - BASED NANOCOMPOSITES AND BIOMOLECULES FOR BONE TISSUE ENGINEERING - Advanced Biomaterials: Fundamentals, Processing, and Applications - page 565

hMSC from vertebral bodies cultured in serum-free conditions seemed to
have preferential response to treatment with certain BMPs, with regards to osteo-
induction. Amongst BMP-2, -4, -6 and -7, BMP-6 appeared to be a potent stimu-
lus of osteoblastic differentiation and its gene expression was detected prior
hMSC osteoblastic differentiation. The incorporation of BMP-6 to hMSC pro-
moted the expression of osteoblastic genes such as Type I collagen, osteocalcin
and bone sialoprotein. Furthermore, it stimulated key osteoblastic transcription
factors such as cbfa-1/RUNX-2 and osterix. The synergistic effects led to an
enhanced mineralization of extracellular matrix and hydroxyapatite deposition.
It was shown that osteogenic growth factors such as IGF-1,

β - fi broblast growth

factor ( -FGF) and VEGF did not have direct osteoinductive effects on hMSC

under serum-free media conditions. It was suggested that the above-mentioned
growth factors, while essential in the function of osteoblasts or pre-osteoblasts
and skeletal development, may not be suffi cient in osteoblastic hMSC differentia-
tion 144 . In a separate study, Boden and his colleagues showed that BMP-6 stimu-
lates induced differentiation readily in rat calvarial cells, without glucocorticoid
potentiation 145 . Similarly, the upregulation of BMP-6 production in rat calvarial
cells in the presence of glucocorticoid was observed 144,146 . Conversely, the lack
of sensitivity to BMP-2 and BMP-4 could be due to the expression of several
families of secreted BMP antagonists, of which these antagonists could have
a high affi nity to BMP-2 and BMP-4, hindering their signaling, unlike BMP-6
and BMP-7 with a lower affi nity to the antagonists 144 . Another explanation as
to the lack of responsiveness of MSCs to certain BMPs could be due to a
dose-dependant issue at which higher doses were essential for the induction of
differentiation 147 .
Surface chemistry was said to infl uence the MSC behavior with silane-
modifi ed surfaces as substrate materials in both basal and stimulated condi-
tions 148 , leading to the importance of studying the minute details of material
science such as surface area, porosity, local acidifi cation, degradation properties,
and so on. This phenomenon also pertains to other cell types.

β

16.4.3 MSCs Derived from Other Sources
Umbilical cord blood (UCB), periosteum, synovium and muscle tissues are some
of the alternate sources whereby MSCs can be derived 149 - 152 . Kern et al. delved
the characteristics of three different tissues (UCB, bone marrow, and adipose
tissue) as a human source of MSCs. There were no signifi cant differences
when morphology (fi broblastoid) and immume phenotype of the MSCs were
concerned. All these sources portrayed a multipotential differentiation ability
with the capability of formation of colony- forming unit - fi broblast (CFU - F) and
expression of a set of surface proteins (e.g. CD44, CD73, CD29, CD90, HLA-1).
The success rate of isolating MSCs was 100% for both the bone marrow and the
adipose tissue samples. Conversely, the isolation rate for umbilical cord blood
was 63% 149 .