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Study Raises Doubt About the Notion of Adult Stem Cell Plasticity

Adult stem cells from bone marrow fail to generate stromal cells after hematopoietic cell transplantation

CHICAGO — Aug. 5, 2002 — Seattle researchers report in the August 2002 issue of Experimental Hematology that adult stem cells that lead to the formation of all blood cells do not, even 27 years after transplantation, contribute to the development of other cell types in the bone marrow, specifically stromal cells, which provide the support structure of the marrow. These findings cast doubt on the notion that adult stem cells, at least those from bone marrow, are as capable of generating a variety of tissues as embryonic stem cells.

Dr. Norihiro Awaya and researchers from the Fred Hutchinson Cancer Center report that non-blood-forming cells in bone marrow called stromal cells exhibit characteristics only of the recipient up to 27 years after successful transplantation of donor bone marrow or blood stem cells.

The researchers studied four patients, three men and one woman, who received bone marrow or blood from a sibling of the opposite sex for the treatment of leukemia or aplastic anemia one to 27 years before the study. Bone marrow and blood contain stem cells whose daughter cells over generations lead to the development of red and white blood cells, lymphocytes and platelets in a process called hematopoietic differentiation.

The research group, under the direction of Dr. Beverly Torok-Storb, hypothesized that if hematopoietic stem cells are "plastic," they would not only generate hematopoietic tissue but also contribute over time to nonhematopoietic tissue elsewhere in the bone marrow, such as stroma. They therefore looked for markers, such as sex chromosomes, to distinguish donor and patient cells.

The researchers found that although the patients' hematopoietic cells in blood and bone marrow could be traced to the donor, the non-hematopoietic stromal cells cultured from their bone marrow were clearly from the patients' own cells. For example, in the female patient who had received bone marrow from her brother, the hematopoietic cells in her bone marrow contained the male Y chromosome but her stromal cells did not.

In previous studies, Dr. Torok-Storb's team showed that stromal cells remain host (the patient's) in origin when evaluated one to three years after donor hematopoietic stem cell transplantation.

The authors conclude that these results suggest that hematopoietic stem cells do not transdifferentiate into bone marrow stromal cells, even after 27 years have elapsed to allow such transdifferentiation to occur, and even when there was a demand for new stroma due to damage from chemotherapy and radiation therapy. The authors caution that it remains to be determined whether this applies to other tissues.

The research was funded by the National Institutes of Health in Bethesda, Md.

Editor's Note
The article appears in the August 2002 issue of Experimental Hematology, a special issue focused on stem cell plasticity and edited by Dr. Catherine Verfaillie, Director of the Stem Cell Institute at the University of Minnesota in Minneapolis. Experimental Hematology is a 30-year-old, peer-reviewed journal published monthly.

To obtain copies of the article, titled "Failure of adult marrow-derived stem cells to generate marrow stroma after successful hematopoietic stem cell transplantation," and contact information for the authors and editors, call Veronica Johnston, Experimental Hematology, at (312) 355-3777.

Media Contact
Susan Edmonds
(206) 667-2896
sedmonds@fhcrc.org

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Fred Hutchinson Cancer Research Center
The Fred Hutchinson Cancer Research Center, home of two Nobel Prize laureates, is an independent, nonprofit research institution dedicated to the development and advancement of biomedical technology to eliminate cancer and other potentially fatal diseases. Fred Hutchinson receives more funding from the National Institutes of Health than any other independent U.S. research center. Recognized internationally for its pioneering work in bone-marrow transplantation, the center's four scientific divisions collaborate to form a unique environment for conducting basic and applied science. Fred Hutchinson, in collaboration with its clinical and research partners, the University of Washington Academic Medical Center and Children's Hospital and Regional Medical Center, is the only National Cancer Institute-designated comprehensive cancer center in the Pacific Northwest and is one of 38 nationwide. For more information, visit the center's Web site at www.fhcrc.org.

Fred Hutchinson Cancer Research Center is a world leader in research to prevent, detect and treat cancer and other life-threatening diseases.