Microenvironment Design for Stem Cell Fate Determination - Tissue Engineering: Cell-Surface Interactions for Tissue Culture - page 233

Fig. 3 Schematic model of the BMP functions in hMSC osteogenic differentiation. In addition to
the BMP-activated osteo-inductive Smad pathway, BMP2 and BMP4 also activate the JAK-
STAT pathway in hMSC through mTOR and ERK1/2 cascades, respectively. The STAT pathway
serves as a negative modulator for BMP-induced hMSC osteogenic differentiation [ 42 ]
Compelling evidence now reveals that stem cell behavior can be fine-tuned by
varying the concentration and combination of the factors of interest. Moreover, the
spatio-temporal context is of great importance, influencing stem cell fate deter-
mination, as further discussed below.
2.2 Synthetic Factors
Synthetic small molecules targeting specific signaling pathways were shown to be
useful in manipulating stem cell fate, by sustaining their pluripotency or inducing
differentiation [ 44 ]. For instance, a small molecule named stauprimide was shown
to increase the efficiency of the directed differentiation of mouse and human ESCs
into endodermal lineages, as pancreatic or hepatic, in synergy with defined
extracellular signaling cues [ 45 ]. In another study, the molecules IDE1 and IDE 2
were also shown to direct endodermal differentiation [ 46 ] of mouse and human
ESCs. Additionally, (-)-indolactam V is a small molecule that directs differenti-
ation of hESCs into the pancreatic lineage [ 47 ].
Small molecules have been shown to replace transcription factors and enhance
efficiency during somatic cell reprogramming (reviewed in [ 44 ]). Small molecules