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New York City
August 2002

Weill Cornell Medical College Advance
Recovery of Adult Bone Marrow Stem Cells for Tissue Regeneration
Edited By Herman Rosen, M.D.

Dr. Shahin Rafii and colleagues from Weill Medical College of Cornell University have discovered the mechanism by which organ-specific adult bone marrow stem cells may be recruited. Stem cells derived from embryos have been the subject of recent ethical debate, but stem cells derived from adult bone marrow may prove to be even more suitable for therapeutic purposes, both as the key to blood vessel formation in tumors and as an alternative source of replaceable stem cells that can be used readily for fighting disease through organ regeneration and gene therapy.

Stem cells derived from bone marrow normally rest there. When stimulated, they proliferate, self-renew, and are mobilized to the peripheral blood, where they incorporate into damaged tissue. The mechanism by which stem cells are stimulated was published in a recent issue of Cell. The research provides enormous promise for the development of far-reaching therapeutics. The newly unlocked mechanism may be the key to facilitating future treatments of countless diseases, ranging from heart disease and stroke to diabetes and Parkinson’s. By stimulating the production of stem cells from the adult bone marrow, thereby facilitating their recovery, doctors may eventually be able to restore the functioning of diseased mature organs such as the heart, muscle, lung, kidneys, pancreas, and brain.

Adult bone-marrow-derived stem cells may have an advantage over embryonic stem cells in that they possess “the appropriate developmental instructions and are more likely to engraft functionally into an adult tissue, undergoing regeneration during development or after injury,” said Dr. Rafii. They found that physiological stress, as may occur during tissue injury, activates an enzyme (called MMP-9) in bone marrow cells, and that promotes the release of Stem Cell Factor which leads to the proliferation and mobilization of stem cells from a dormant microenvironment of the bone marrow to an environment that promotes their expansion, differentiation, and mobilization to the bloodstream.

These exciting results lay the foundation for developing strategies whereby activation of enzymes such as MMP-9 or others can function as molecular switches to expand and recover a large population of hibernating stem cells for use in tissue-regeneration and gene therapy.#

Dr. Herman Rosen is Clinical Professor of Medicine at Weill Medical College of Cornell University.

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