274 
Monitoring Stem Cell Research 
derived from interspecific crosses, and abnormal gene expression in 
mice derived from ES cell nuclear transfer. 
The results of the study by Onyango et ai. utilizing EG cell lines 
derived at John Hopkins, clearly demonstrate that general 
dysregulation of imprinted genes will not be a barrier to their use in 
transplantation therapies. The report has determined that the EG 
cells are not imprinted, that is, imprinting has been erased in the 
primordial germ cells that gave rise to the EG cells, that the erasure 
is maintained in the EG cells, but in all informative cases, they 
observed the transcription of only a single allele in differentiated 
cells derived from the human EG cells. These results, although on a 
limited number of lines and only a few imprinted genes, would 
indicate that these human EG cell lines will serve as reliable and safe 
sources for the study of EG cell differentiation and, perhaps, cells for 
cell-based interventions. 
Another area of interest in genetic regulation within EG cells is that 
of X inactivation, the mammalian method for equalization of the 
dosage of X-linked genes in males and females. This equalization is 
accomplished by the down regulation of the transcriptional output of 
the X chromosomes in females, so that only one X is active in diploid 
somatic cells of both sexes. Inactivation is initiated in female 
blastocysts. Both X chromosomes in female primordial germ cells are 
active. Migeon et al. (2001) have demonstrated that in the very early 
stages of differentiation of cells from human EGs, only one X 
chromosome is active, indicating normal genetic regulation has 
occurred. In a report by Nesterova et al. (2002) on the use of mouse 
female EG cells in the study of X chromosome 
inactivation/reactivation during primordial germ cell migration and 
EG cell formation. Both X chromosomes appear to be active in XX EG 
cells, and presumably, one becomes inactive when cells differentiate 
from the EG cells. 
One of the goals of stem cell research is to provide sources of cells for 
cell-based therapies. As a step in this direction, proof of concept or 
proof of principle studies involve the use of human cells in animal 
models of human disease or injury. Although few, if any, animal 
models are true models for the human diseases, they are the closest 
approximation that can be made. The first report on the use of cells 
derived from stem cells of human embryonic sources was recently 
published: Kerr et al. Human Embryonic Germ Cell Derivatives 
Facilitate Motor Recovery of Rats with Diffuse Motor Neuron Injury, J. 
Neuroscience 23, June 15, 2003. This is the first demonstration that a 
PRE -PUBLICATION VERSION 
