Biomedical Engineering Reference
In-Depth Information
41.2.1.1 Fibroblast growth factors
The FGF family is comprised of 22 growth factors that regu-
late multiple biological processes, including bone and cartilage
formation.
53
Individual FGFs bind to specific receptors or heparin-
like proteoglycans
54
and activate signaling pathways in the cell,
such as the Ras/extracellular-regulated kinase (ERK) and the
phosphatidylinositol 3-kinase (PI3K)/protein kinase B/Akt (AKT)
pathways.
55
Among the members of the FGF family, FGF-2 exerts
the strongest influence on the self-renewal and growth capacity of
MSCs. FGF-2 can accelerate the proliferation of bone marrow MSCs
in vitro
.
56
-
58
However, the effect of FGF-2 on MSC proliferation is
variable,dependingoncultureconditionanddosage.
59
Alowdoseof
FGF-2 (3 ng/mL) induces proliferation of MSCs, but higher doses of
FGF-2 (30 ng/mL) do not. In addition, FGF-2-stimulated MSC prolif-
erationismoree
cientatlowcelldensitythanathighcelldensity.
58
Therefore,stimulationwithlowdosesofFGF-2seemstobeeffective
for the
in vitro
expansion of MSCs cultured at a low cell density. FGF
also appears to induce commitment of MSCs toward an early stage
of the osteoblast lineage. FGF-2-expanded MSCs can induce higher
mineralization
in vitro
and increased bone formation
in vivo
.
56
In
MSCs that have been cultured for multiple passages, the addition of
FGF-2 can help to preserve a normal growth rate
60
and also induces
the expression of FGF in MSCs, which allows them to maintain their
self-renewal potential
in vitro
.
61
These results suggest that FGF-2
can induce the commitment of MSCs to an early or immature stage
of the osteoblast lineage, but those MSCs still retain their potential
for self-renewal.
In addition to FGF-2, other members of the FGF family, includ-
ing FGF-1, FGF-4, and FGF-8, may also stimulate the growth of
MSCs
40
,
62
,
42
41.2.1.2 Epidermal growth factor
EGF has been implicated in the regulation of various cellular
responses. The binding of EGF to its receptor (EGFR) activates
numerous intracellular signaling molecules such as ERK, PI3K/AKT,
Search WWH ::
Custom Search