Researchers Discover Adult Stem Cells in Blood Capable of Generating Organ Tissue

Researchers at The University of Texas M.D. Anderson Cancer Center have shown that human adult stem cells circulating in the blood are capable of differentiating into various organ systems, as reported in the March 7 issue of the New England Journal of Medicine.

These findings suggest that circulating stem cells play an active role in replacing normal tissue or repairing injured tissue of various organs, say the principal investigators Drs. Martin Körbling, Ruth Katz, and Zeev Estrov.

"For years, the school of thought was that when tissue was injured, the repair came from the tissue itself," said Dr. Körbling, professor in M.D. Anderson’s department of blood and marrow transplantation, and lead author of the paper. "But by showing clear evidence of donor-derived cells in the liver, skin and gastrointestinal tissue of patients who underwent stem-cell transplantation, we can prove the existence of a systemic supply of stem cells distributed via the blood that are capable of tissue repair."

"It’s a simple concept, but a concept that makes a huge difference," Dr. Estrov, professor in the department of bioimmunotherapy at M.D. Anderson, said. "The significance is that this leads us into new knowledge of what happens in the body without intervention. If peripheral blood stem cells are capable of differentiating into different organs, this may affect the treatment of many diseases," he said.

The existence of stem cells that could differentiate into bone, cartilage, fat and muscle has been previously identified in human bone marrow. Recently, bone-marrow-derived stem cells have been shown to differentiate into epithelial cells of the skin, lungs and gastrointestinal tract in animal studies.

"But unlike bone marrow stem cells, circulating stem cells can be easily collected from the blood by a routine blood-banking procedure known as apheresis," Dr. Körbling said. "So it is conceivable that adult peripheral blood stem cells could be used clinically for repairing injured tissue or even replacing diseased tissue."

Efforts are already under way to further characterize these stem cells for use in clinical trials, Dr. Estrov said.

The idea for the research came about when two independent clinical studies recently reported that donor-derived hepatocytes (liver cells) were found in patients who had received bone marrow transplants. Drs. Körbling and Estrov hypothesized that since the bone marrow was not in direct physical contact with the liver, GI tract and skin, the circulating blood might be the "vehicle" that contains and distributes stem cells capable of differentiating into various organ cells.

To test their hypothesis, the investigators examined tissue from female patients who had received transplants from a male sibling to see if male chromosomes could be identified in the female’s hepatocytes and epithelial cells of the skin and gut.

They studied tissue specimens from 12 patients who underwent stem cell transplantation from circulating blood or from bone marrow. Six of the patients evaluated had received the sex-mismatched transplants (male into female). Six other control patients received sex-matched stem cell transplants.

Using sophisticated fluorescence staining techniques developed in Dr. Katz’s laboratory, donor-derived male (XY-positive) cells were detected in the female patients’ liver, skin and gut tissue at a frequency of up to 7 percent, and up to one year after transplantation.

"The next step will be to learn the trigger mechanisms that reprogram these circulating stem cells to become various organ cells," Dr. Estrov said.

Potential trigger mechanisms could be tissue damage from high-dose radiotherapy or chemotherapy, and graft-versus-host disease, or GVHD, following stem cell transplantation, he said.

"However, the preliminary data in this study suggests that the epithelial cell engraftment is rather uniform – without preferential location – and doesn’t depend on such parameters as organ specificity or GVHD-induced tissue injury, " Dr. Estrov said.

"We don’t know yet whether these adult blood stem cells have properties that are similar to embryonic stem cells," Dr. Körbling said. "There is no comparative study. Our findings constitute the first clinical evidence that circulating donor-derived stem cells generate organ-specific cells in humans."

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©2006 Texas Medical Center

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