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Mechanism For Regulation Of Adult Stem Cells Found

In a tantalizing possibility for public health, scientists envision a renewable source of functional human replacement cells.

Those cells would be used to treat a multitude of diseases and conditions including Parkinson's and Alzheimer's diseases, heart disease, spinal cord injury, stroke, burns, diabetes and arthritis.

This vision has fueled research efforts to harness the special cells called stem cells that have the ability to develop into almost any kind of human tissue.

The use of human embryonic stem cells has been confronted with major obstacles because of bio-ethical and political issues involved obtaining them, as well as the suggestion that embryonic stem cells may lack appropriate developmental instructions, making them potentially less feasible for engrafting into adult tissue.

One alternative source of stem cells is adult bone marrow. However, the use of stem cells from adult bone marrow has been hampered by the lack of knowledge regarding the mechanism by which these cells are recruited from the bone marrow and mobilized to the peripheral blood from which they can be incorporated into damaged tissue.

Now, a group of scientists from Cornell University Medical College have identified and described a novel mechanism by which bone marrow-derived stem cells are stimulated to divide and mobilize to the peripheral circulation.

This research, published in today's issue of Cell, provides enormous promise for the development of far-reaching therapeutics.

Dr. Shahin Rafii and colleagues demonstrate that physiological stress results in the activation of an enzyme referred to as metalloproteinase-9 (MMP-9) in the bone marrow cells. They report that MMP-9 deficient mice, despite having no apparent defects, failed to recover after receiving high doses of chemotherapeutic agents. Compared to control mice, over 70% of the mice deficient in MMP-9 died from complications of marrow suppression.

This finding suggests that activation of MMP-9 may be essential for renewal of blood stem cells. Drs. Heissig and Hattori from Dr. Rafii's group and colleagues from UCSF went on to demonstrate that activated MMP-9 promotes the release of a molecule called Kit-ligand (sKitL).

Activated sKitL increases the mobility of stem cells from the bone marrow niche, thereby moving them to a permissive environment that is conducive to expansion and mobilization to the peripheral blood.

These exciting results lay the foundation for developing strategies in which activation of enzymes such as MMP-9 act as molecular switches to expand a large population of stem cells that may ultimately be used for tissue regeneration.

As compared to embryonic stem cells, adult derived stem cells are endowed with additional developmental instructions and may be better suited for therapeutic purposes.

According to Dr. Rafii, "We are approaching a day when a patient's own stem cells can be induced to divide and develop into tissue that can replace that which is diseased or destroyed, making overcrowded organ transplant lists and rejection of foreign tissues a thing of the past."

[Contact: Dr. Shahin Rafii]






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