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Differential bone marrow stem cell mobilization by G-CSF injection or arterial ligation in baboons

Shi et al. J Cell Mol Med. 2009 Aug;13(8B):1896-906

Tissue injury is known to cause stem cells to exit the bone marrow, where they normally reside, and enter into circulation, apparently en route to attempt to repair the area of injury.  This concept has been demonstrated in patients with heart attacks, in that following damage to the heart muscle, an increased number of stem cells is observed in circulation, as is described in this video http://www.youtube.com/watch?v=NqEggEYilh0.  The same holds true in patients with stroke, in that after a stroke, there is an association between higher number of endothelial progenitor cells (a type of stem cell that gives rise to blood vessels), and positive neurological outcome (Dunac et al. Neurological and functional recovery in human stroke are associated with peripheral blood CD34+ cell mobilization. J Neurol. 2007 Mar;254(3):327-32).  This is one of the reasons why patients take nutritional supplements such as Stem-Kine that increase the numbers of stem cells in circulation.

In a recent study from the Department of Genetics, of the Southwest Foundation for Biomedical Research, in San Antonio, Texas researchers attempted to dissect specifics of how tissue damage increases the number of circulating stem cells.  Since heart attacks and strokes occur in different degrees of severity in people, the scientists used a reproducible model of tissue injury in baboons.  They blocked circulation to part of the leg by tying off the femoral artery.  As a comparator approach, they injected other baboons with the drug granulocyte colony stimulating factor (G-CSF) which is currently used by hematologists to "harvest" stem cells from the blood of stem cell donors. 

In baboons receiving G-CSF and the group inflicted with circulation blockade, the increase in stem cells in circulation peaked at day 3.  The stem cells expressing CD34 were twice as high in the circulation of animals that received G-CSF as compared to the animals with ligated femoral artery.  In contrast, another type of stem cell, the CD133+/KDR+/CXCR4+/CD31+ cell, which represents endothelial progenitor cells, was detected at higher levels in ligated animals as compared to G-CSF treated animals.  When these cells were grown in tissue culture plates, they resembled functional blood vessel cells called "endothelium"

This study suggests that different types of stem cells are "told" by conditions in the body to leave the bone marrow and to go into circulation.  Given that ligation of an artery is expected to cause damaged to the endothelium, it is conceivable that the release of endothelial progenitor cells is occurring in order for the body to attempt to heal injured tissue.  If this concept is correct, it will be interesting to see if the stem cells that increase in circulation in patients with a heart attack have a propensity to become heart cells when placed in tissue culture.  The other interesting point raised by this study is whether chemicals can be administered that would assist the body in increasing the number of the proper type of stem cell in circulation after injury.



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