AN EFFICIENT EX VIVO EXPANSION OF ADULT MESENCHYMAL STEM CELLS IN SCAFFOLDS - Intelligent Scaffolds for Tissue Engineering and Regenerative Medicine - page 845

differentiation because MSCs expanded with FGF-2 and dexametha-
soneexpress ALP.
Because the effect of FGF-2 on MSC proliferation is more
prominent at low cell density than at high density, enhanced bone
formation can be achieved by seeding of low numbers of MSCs into
a scaffold followed by culture for a given period in the presence of
FGF-2 and dexamethasoneprior to use.
41.4 Conclusions and Outlook
This article has focused on the ex vivo expansion of MSCs for their
useinthetherapeuticregenerationofbonedefects.Inaddition,sev-
eralfactorsthatmodulatetheproliferativepotentialofMSCs,suchas
donor age, plating density, serum type, and the presence of growth
factors, 31 were also discussed. Of these, growth factors have the
strongest effect on MSC proliferation. In particular, FGF-2, EGF, and
PDGF, either alone or in combination with glucocorticoids such as
dexamethasone, strongly induce the proliferation of MSCs. Thus, a
combination of growth factors and glucocorticoids may provide the
optimal conditionsforthe expansion of MSCs in vitro .
However, other aspects of ex vivo expansion of MSCs with
growth factors and glucocorticoids can induce both osteoblast
and adipocyte lineage commitments, as revealed in articles by
Lee and Locklin. 43 , 44 Because osteogenic differentiation occurs at
the expense of adipocyte lineage commitment, any molecules that
suppress adipogenic differentiation can potentiate the osteoblast
lineage commitment of MSCs, while maintaining their proliferative
potential. In fact, administration of a PPAR γ antagonist during MSC
expansion with FGF-2 and dexamethasone significantly stimulated
both proliferation and osteoblast differentiation. 109 Examining the
effects of other suppressors of adipogenic differentiation may pro-
vide relevant information about ex vivo expansion, osteoblast com-
mitmentof MSCs, and in vivo boneformation.
Because expansion of MSCs under culture conditions free
of animal-derived serum is also critical for their therapeutic
application, 111 , 112 it is of great importance to use a combination
of growth factors or growth factors with glucocorticoids to ensure