AN EFFICIENT EX VIVO EXPANSION OF ADULT MESENCHYMAL STEM CELLS IN SCAFFOLDS - Intelligent Scaffolds for Tissue Engineering and Regenerative Medicine - page 842

lipiddroplets. 43 , 44 TheseresultssupportthatFGF-2anddexametha-
sone can induce both osteoblast and adipocyte lineage commitment
of MSCs. Under conditions in which PPAR γ has been suppressed by
an antagonist, the combination of FGF-2 and dexamethasone fur-
ther stimulates proliferation and osteoblast lineage differentiation
in vitro . 109 It will be interesting to determine whether the combina-
tion of FGF-2, dexamethasone, and PPAR γ antagonist (or other adi-
pogenesis inhibitors)can promote boneformation in vivo .
Although the mechanism underlying the enhanced proliferation
andosteogenicdifferentiationinducedbyFGF-2anddexamethasone
is largely unknown, Src kinase is likely to be involved in this event.
In response to FGF-2 and dexamethasone, phosphorylation of c-Jun
N-terminal kinase, ERK, and p38 MAPK is decreased, while stimula-
tory tyrosine phosphorylation of Src kinase is increased, suggesting
the involvement of a Src-dependent pathway in the enhanced pro-
liferation of MSCs. Moreover, Src family kinase inhibitors substan-
tially reduce FGF-2 and dexamethasone-induced proliferation and
osteoblastlineage differentiation of MSCs. 43
Gronthos and Simmons have demonstrated that a combination
of growth factors can also stimulate the growth of MSCs. Simul-
taneous addition of PDGF and EGF resulted in dose-dependent
increases in mean colony diameter, indicating enhanced growth of
MSCs. Therefore, EGF/EGFR and PDGF/PDGFR signaling may coop-
erate to induce a synergistic induction of MSC proliferation. 80 In
another study by Ng et al .,thecombinationofPDGF, TGF- β ,andFGF
was shown to be su cient to induce MSC growth in a serum-free
medium for up to five passages. Inhibiting any one of these path-
ways reduced MSC growth, demonstrating the importance of these
three factors for the growth of MSCs. 110 These results are particu-
larly significant, because elimination of animal-derived culture sup-
plements is one of the challenges facing effective MSC expansion
in vitro .
41.3 GrowthofMSCsinScaffolds
Inordertoregeneratedamagedtissues,MSC-loadedscaffoldscanbe
either directly transplanted or cultured for an appropriate length of