Research and Therapy Developments 
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IV. BASIC RESEARCH USING HUMAN STEM CELLS 
Human stem cells are proving useful in basic research in 
several ways. They are useful in unraveling the complex mo- 
lecular pathways governing human differentiation. For exam- 
ple, because ESCs can be stimulated in vitro to produce more 
differentiated cells, this transition can be studied in greater 
detail and imder better-controlled conditions than it can be in 
vivo. In the best circumstances, these differentiated cells can 
be grown as largely homogeneous cell populations, and their 
gene expression profiles can be compared in detail. 
Also, stem cell preparations can be used to produce popula- 
tions of specialized cells that are not easily obtained in other 
ways. In one case, for example, this approach has provided 
large quantities of human trophoblast-like cells that have not 
been previously available. In addition, cultures of differenti- 
ated cells derived from stem cells could be used to test new 
drugs and chemical compounds for toxicity and mutagenicity .^^ 
As experience with these differentiated derivatives of human 
ESCs grows, it may become possible to reduce or eliminate the 
use of live animals in such testing protocols. 
In the near future, the differentiated state of various human 
cell types will be characterized not just by a few biological 
markers, but by the pattern and levels of expression of hun- 
dreds or thousands of genes. Integration of this knowledge 
with the catalog of all human genes produced during the Hu- 
man Genome Project will gradually give us knowledge of 
which genes are key regulators of human development and 
which genes are central to maintaining the stem cell state.” 
Increased understanding of the molecular pathways of human 
cell differentiation should eventually lead to the ability to di- 
rect in vitro differentiation along pathways that yield cells use- 
ful in medical treatment. In addition, when the normal range of 
gene expression patterns is known, researchers can then de- 
termine which genes are expressed abnormally in various dis- 
eases, thus increasing our understanding of and ability to treat 
these diseases. 
A group of stem cell researchers has recently outlined a set 
of important research questions, which, once answered will 
greatly enhance our understanding of human embryonic stem 
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