Biomedical Engineering Reference
In-Depth Information
Quarto
et al.
have demonstrated exciting results regarding the
combination of growth factors and glucocorticoids in human bone
marrow MSCs.
45
The osteogenic and proliferative potentials of
human bone marrow MSCs are dramatically increased in response
to dexamethasone combined with FGF-2. Both CFU-F size and
proliferationofMSCsaresignificantlyhigherinthepresenceofcom-
bined FGF-2 and dexamethasone,
44
-
46
suggesting that a combina-
tion of cell-proliferative factors and osteogenic factors amplifies the
proliferation potential in bone marrow MSCs. The combination of
FGF-2 with other glucocorticoids, such as betamethasone, dexam-
ethasone, hydrocortisone, and prednisolone, reveals that hydrocor-
tisone and prednisolone do not exert strong cooperative effects on
MSC proliferation but that betamethasone and dexamethasone are
ableto stimulate their proliferation.
43
In addition, while dexamethasone alone increases levels of ALP,
a key enzyme that mediates the mineralization process, a com-
bination of FGF-2 and dexamethasone down-regulates ALP levels
by 56%. This indicates that FGF-2 signaling can partially suppress
dexamethasone-induced osteogenic differentiation. This indicates
that in the presence of FGF-2, dexamethasone cannot further the
differentiation of MSCs and thus maintains them at an early stage
of commitment. Interestingly, after subcutaneous implantation into
nudemice,MSCsthathadbeenexpandedinculturewithacombina-
tionofFGF-2anddexamethasonewereabletoformmorebonethan
those expanded with either FGF-2 or dexamethasone alone. There-
fore, osteogenic-specific priming of MSCs to the immature stage
appearstoinduceenhancedboneformation.Enhancedproliferation
and osteoblast differentiation in response to FGF-2 and dexametha-
sone are not restricted to human bone marrow MSCs; these effects
have been observed in other tissue- and species-derived MSCs, such
as rat bone marrow MSCs,
107
equine MSCs,
108
and human adipose
tissue-derived MSCs.
43
At the same time, a combination of FGF-2 and dexamethasone
at the dosage used for induction of proliferation and osteoblast
differentiation can also induce adipocyte lineage commitment.
43
,
44
FGF-2 and dexamethasone induce expression of ALP as well as per-
oxisome proliferator-activated receptor
γ
(PPAR
γ
), an adipocyte
marker in adipose-derived MSCs,
43
and enhance the formation of
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