AN EFFICIENT EX VIVO EXPANSION OF ADULT MESENCHYMAL STEM CELLS IN SCAFFOLDS - Intelligent Scaffolds for Tissue Engineering and Regenerative Medicine - page 838

41.2.1.3 Platelet-derived growth factor

PDGF exists as four subtypes (PDGF-A, -B, -C, and -D) and acts
as homo- or heterodimers to stimulate their specific receptors,
either PDGFR α or β . 74 The activated PDGFRs, which are tyro-
sine phosphorylated in their cytoplasmic domains, recruit adap-
tor proteins and activate several signaling pathways, such as
Ras-ERK, PI3K/Akt, and phospholipase C γ . 75 Consequently, PDGFs
are able to potently modulate biological responses, such as prolif-
eration of mesenchymal cells and the regulation of wound-healing
processes. 76
PDGFRs are found to be expressed in MSCs, 77 and binding
of the PDGF-BB homodimer to its receptor strongly induces the
proliferation and migration of MSCs. 41 , 71 , 78 Inhibition of PDGFR β
by imatinib mesylate suppresses proliferation of human MSCs in
vitro , 41 , 78 suggesting that PDGFR signaling may mediate PDGF-

induced proliferation of MSCs. Recently, a study conducted in
PDGFR

β

β

-impairedmicedemonstratedthatthemitogenicandmigra-
tory responses of MSCs to PDGF are dramatically reduced, while
osteogenicdifferentiationisenhanced. 79 Therefore,PDGFR

β

signal-
ing appears to elicit opposing responses with regard to prolifera-
tion and osteoblast lineage differentiation in MSCs. In comparison
to the effects mediated by PDGFR β , the influence of PDGFR α on
osteogenic differentiation is very subtle. 79 The stimulatory effect of
PDGF on the proliferation of MSCs is demonstrated by the clono-
genic growth of bone marrow MSCs. Both PDGF-BB and EGF show a
strong ability to enhance clonogenic growth of CFU-F under serum-
deprived culture conditions. 80 In addition, although a combina-
tion of growth factors, such as EGF, FGF-2, and PDGF, does not
induce a significant increase in colony numbers, dose-dependent
increases in mean colony diameter suggest a synergistic effect
on cell proliferation. 80 Interestingly, the enhanced colony forma-
tion of MSCs by PDGF that occurs in a serum-free medium is not
observed in a medium containing 10% serum. 56 Therefore, PDGF,
PDGF-BB in particular, is able to induce proliferative and migra-
tory responses but strongly inhibits osteogenic differentiation of
MSCs.