Molecular mechanism found that may improve ability of stem cells to fight disease

Findings published in current issue of Nature Cell Biology

Adult stem cell transplantation offers great therapeutic potential for a variety of diseases due to their ability to replenish diseased cells and tissue. While they are unique in this ability, it remains a challenge to effectively treat disease long-term with stem cells because of our inability to grow them in the laboratory. Defining the molecular switch in the stem cell replication process, or cell cycle, is a key step to stimulating their growth for broader clinical use.

In the May issue of Nature Cell Biology, Tao Cheng, M.D., assistant professor, department of radiation oncology, University of Pittsburgh School of Medicine, and colleagues report the discovery of a molecular mechanism in the cell cycle that appears to impact the replicating ability of stem cells from bone marrow and blood to fight disease. They found that blood stem cells from mice missing a gene called p18 were much better able to multiply and grow. p18 is a molecule in a class of so-called “cyclin-dependent kinase inhibitors” that are critical inhibitors of cell cycle control.

In the study, Dr. Cheng and his team isolated p18-deficient stem cells from mice and found that these cells were much more efficient at repopulating injured bone marrow tissue. As a result, they concluded that blocking the function of p18 may be a productive way to enhance the efficacy of stem cell transplantation as a treatment for diseases.

“Stem cells have great potential, but we need to develop novel strategies to help them proliferate to better fight diseases,” said Dr. Cheng, also stem cell biologist at the University of Pittsburgh Cancer Institute. “By using stem cells deficient in p18, we found a strikingly improved long-term engraftment of stem cells in bone marrow leading us to the conclusion that p18 is a strong inhibitor to stem cell self-renewal. This is an exciting finding because it may lead to a new medical invention that can improve the ability of stem cells to self-renew, and thus, more effectively treat a wide range of diseases including cancer.”

Stem cells give rise to blood cells with various essential functions, from carrying oxygen to providing immunity against disease. Preserving the function of stem cells and correcting any defects is essential to fighting disease and maintaining health. Stem cell transplantation is a common treatment for patients with advanced or recurrent cancers of the blood, such as leukemia and lymphoma.

The study was funded in part by grants from the National Institutes of Health. Co-first-authors include Youzhong Yuan, M.D., Ph.D., and Hongmei Shen, Ph.D., at the University of Pittsburgh Cancer Institute. Other collaborators and co-authors include David S. Franklin, Ph.D., Purdue University and David T. Scadden, M.D., Massachusetts General Hospital and Harvard Medical School.

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