AN EFFICIENT EX VIVO EXPANSION OF ADULT MESENCHYMAL STEM CELLS IN SCAFFOLDS - Intelligent Scaffolds for Tissue Engineering and Regenerative Medicine - page 839

41.2.1.4 Other growth factors

Other growth factors have also been implicated in regulation of
the proliferative potential of MSCs. BMP-2, a member of the TGF-
β superfamily, exerts a suppressive effect on MSC proliferation.
BMP-2 antagonizes Wnt3a signaling and inhibits the proliferation
of mouse bone marrow MSCs through the interaction of the BMP
receptor, Smad, with Dishevelled-1, which is a component of the
Wnt-signaling pathway. 81 Conversely, TGF- β 1 induces the prolif-
eration of human MSCs, through both Smad3-dependent nuclear
accumulation of β -catenin and activation of the Smad-independent
Ras-ERKsignalingpathwayinMSCs. 82 , 83 Therefore,TGF- β signaling
may regulate MSC proliferation through crosstalk with the Wnt sig-
naling pathway. 84
IGF-1 is potentially capable of stimulating proliferation of
MSCs, 85 , 86 but this effect is not reliably reproducible. 87 Prolifera-
tion of MSCs has also been shown to be influenced by HGF, TGF-
α α

, IGF-2, stem cell factor, and a number of
other growth factors. 7 , 86 , 88 , 89

, tumor necrosis factor-

41.2.2 Glucocorticoids
Glucocorticoids play an important role in bone metabolism
by regulating the activities of osteoblasts and osteoclasts. In
particular, glucocorticoids regulate osteoblast and adipocyte lin-
eage commitment. 90 - 92 Transgenic mice that overexpress 11 β -
hydroxysteroid-dehydrogenase type 2 (11 β HSD2), an enzyme that
catalyzes the conversion of active cortisol to inactive cortisone, 93 - 95
reveal phenotypic impairments in bone, such as vertebral osteope-
nia, reduced femoral cortical bone area and thickness, delayed cra-
nial bone formation and suture closure, and impaired mineralized
nodule formation of primary calvarial cells. 95 , 96 These phenotypic
impairments appear to be due to a defect in Wnt signaling, which
normally stimulates osteoblast lineage commitment of MSCs. 92 , 96
These observations underscore the important role that glucocorti-
coids play during normal bonedevelopment.
Glucocorticoids are commonly prescribed drugs used
under a variety of circumstances, including organ transplantation,