Appendix I. 
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cells should offer an improved supply of neural tissue, for both in 
vitro experimental studies and transplantation therapies. 
Human ES cell-derived embryoid bodies produce both neural 
precursor cells and cells expressing markers of mature neurons and 
glia [26-29]. The percentage of neural precursors can be enriched by 
alteration of culture conditions [26-28] or by purification using cell 
surface markers [28]. Human ES cell-derived neural cells are able to 
synthesize and respond to neurotransmitters, form synapses and 
voltage-dependent ion channels capable of generating action 
potentials, and generate electrical activity [28]. Some human ES cell- 
derived neurons express tyrosine hydroxylase, the rate-limiting 
enzyme involved in dopamine synthesis and a marker of 
dopaminergic neurons [26, 27]. 
Human ES cell-derived neural precursors transplanted into 
the mouse brain differentiate into all three types of central nervous 
system cells (neurons, glia cells, and oliogodendrocytes) [26, 27]. 
These differentiated cells migrate, following host developmental 
cues, into various areas of the brain (including cortex, hippocampus, 
striatum olfactory bulb, septum, thalamus, hypothalamus, and 
midbrain) [26, 27]. One of the concerns about using human ES cell- 
derived neural cells in transplantation therapy is the fear that 
undifferentiated ES cells may be transplanted with the differentiated 
cells and form teratomas in the host. To date, transplantation of 
isolated, human ES cell-derived neural precursor cells into mice has 
not produced teratomas [26, 27], suggesting that appropriate 
selection procedures can eliminate undifferentiated ES cell 
contamination. However, longer-term testing is still needed to 
address the teratoma formation issue more carefully. 
Hematopoietic Differentiation 
Human ES cells are already providing a sustainable source of 
hematopoietic cells for in vitro studies [36, 37]. Hematopoietic stem 
cells are by far the most studied adult stem cells, and bone marrow 
transplants are the most common and effective form of stem cell- 
based therapy. However, despite several decades of research by 
hundreds of laboratories, hematopoietic stem cells have not yet been 
successfully expanded in clinically useful amounts, and these cells 
must instead be transferred directly from the donor. When cultured 
in vitro, hematopoietic stem cells do not self-renew, but instead 
differentiate to specific blood cells, and thus quickly disappear. This 
makes the in vitro study of human hematopoiesis difficult, as 
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