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Monitoring Stem Cell Research 
lung is lower (unpublished observations). Noteworthy is the fact that 
neither mouse nor human MAPC appear to contribute to other 
tissues when injected IV, except to endothelium (see below). 
Although PCR analysis for human DNA in human - mouse 
transplants or for 0-galactosidase in mouse-mouse transplants 
yielded positive signals in many tissues, we believe that this is 
mainly due to contaminating blood cells. When tissues were carefully 
examined for tissue specific differentiated MAPC progeny, we could 
not detect MAPC-progeny in brain, skeletal muscle, cardiac muscle, 
skin or kidneys. Lack of engraftment in brain, skeletal and cardiac 
muscle may be due to the fact that transplants were done in non- 
injured animals, where the blood brain barrier is intact, and where 
little or no cell turnover is expected in muscle. More difficult to 
explain is the absence of MAPC-derived progeny in skin, possibly the 
organ with the greatest cell turnover. Studies are ongoing to trace 
the homing behavior of MAPC following infusion in non-injured 
animals and injured animals, which may shed light on these 
observations. 
In vivo differentiation into skeletal muscle: 
Muguruma et al have also shown that undifferentiated 
human MAPC injected in the muscle of non-obese diabetic (NOD)- 
SCID mice differentiate into cells that stain positive for muscle 
transcription factors and muscle cytoskeletal proteins (manuscript 
submitted). Similar results were seen in Minnesota. We also found 
that pre-treatment of human MAPC with 5-azacytidine, required to 
induce muscle differentiation in vitro, enhanced the degree of 
engraftment of human cells in mouse muscle, suggesting that pre- 
differentiation of MAPC may imder certain circumstances enhance 
the level of engraftment (unpublished observations). 
Contribution to endothelium in vivo: 
When endothelial cells generated from human MAPC by 
incubation in vitro with vascular endothelial growth factor (VEGF) ® 
were infused in animals in which a tumor had been implanted 
underneath the skin, we detected enhanced tumor growth and found 
that up to 30% of the tumor vasculature was derived from the human 
endothelial cells. Likewise, wounds in the ears of these animals as a 
result of ear tagging contained human endothelial cells. One of the 
animals developed a host-tumor, an occurrence seen frequently in 
aging NOD-SCID mice. We detected contribution of MAPC-derived 
endothelium to tumor vessels Likewise, one of the NOD-SCID mice 
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