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Monitoring Stem Cell Research 
stimuli was associated with activation of transcription factors known 
to be important in neural commitment in vivo and differentiation from 
NSC and mES cells in vitro. Cells staining positive for astrocyte, 
oligodendrocyte and neuronal markers were detected. Neuron-like 
cells became polarized, and as has been described in most studies in 
which ES cells or NSC were differentiated in vitro to a mid-brain 
neuroectodermal fate using FGF8 and SHH, approximately 25% of 
cells stained positive for dopaminergic mairkers, 25% for serotonergic 
markers, and 50% for GABA-ergic markers. Subsequent addition of 
astrocytes induced further maturation and prolonged survival of the 
M ARC -derived neuron-like cells, which now also acquired 
electrophysiological characteristics consistent with neurons, namely 
voltage gated sodium channels and synaptic potentials 
Muscle differentiation: 
In addition, we now have convincing evidence that MAPC 
can differentiate into cells vrith phenotypic as well as functional 
characteristics of smooth muscle cells (manuscript in preparation). 
Interestingly, the lineage that continues to be elusive is cardiac 
myoblasts, despite the fact that mouse MAPC injected in the 
blastocyst contribute to the cardiac muscle Although a number of 
in vitro differentiation conditions induce expression of Nkx2.5, 
GATA4, and myosin heavy chain mRNA and proteins we have 
been unable to induce differentiation of MAPC to cells with the 
typical functional characteristic of cardiac myoblasts, i.e. 
spontaneous rhythmic contractions or beating, a differentiation path 
that is almost a default differentiation pathway for mouse ES cells. 
The reason for the lack of functional cardiac myoblast properties is 
currently unknown. 
Another important cell lineage that has not yet been generated is 
insulin-producing cells, even though initial studies suggest that 
differentiation to cells expressing at least early pancreatic and 
endocrine pancreas transcription factors can be obtained. 
In vitro differentiation of MAPC as model system for gene 
discovery: 
A last comment regarding in vitro differentiation of MAPC is 
that, in contrast to differentiation of ES cells in vitro, the final 
differentiated cell product derived from MAPC is commonly >70-80% 
pure. This should allow using these in vitro differentiation models for 
gene and drug discovery. For instance, in a recently published study 
we compared the expressed gene profile in human MAPC induced 
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