Science Article from Stanford Medical School

Amy J. Wagers[*], Richard I. Sherwood, Julie L. Christensen, and Irving L. Weissman, "Little Evidence for Developmental Plasticity of Adult Hematopoietic Stem Cells," Published online September 5, 2002; 10.1126/science.1074807 (Science Express Reports)

Department of Pathology and Department of Developmental Biology, Stanford University School of Medicine, Stanford, CA 94305, USA.

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To rigorously test the in vivo cell fate specificity of bone marrow (BM) hematopoietic stem cells (HSCs), we generated chimeric animals by transplantation of a single green fluorescent protein (GFP)-marked HSC into lethally irradiated nontransgenic recipients. Single HSCs robustly reconstituted peripheral blood leukocytes in these animals, but did not contribute appreciably to nonhematopoietic tissues, including brain, kidney, gut, liver, and muscle. Similarly, in GFP+:GFP- parabiotic mice, we found significant chimerism of hematopoietic but not nonhematopoietic cells. These data indicate that "transdifferentiation" of circulating HSCs and/or their progeny is an extremely rare event, if it occurs at all.

Adult Stem Cells a Bust?

September 9, 2002; Washington, D.C. ( CNN and AP) -- Adult blood stem cells were unable to transform into other types of tissue cells in a Stanford University study, raising new doubts about the eventual value of the cells in the treatment of disease. "The finding supports the view that embryonic stem cells, not adult stem cells, offer the most promise for treating conditions such as heart disease, spinal injury, diabetes, and Parkinson's Disease," some researchers say.

But many people, including President George W. Bush, oppose using human embryonic stem cells in medical research because it involves the death of an embryo. The Stanford researchers attempted to trace the evolution of blood stem cells after placing them singly into mice whose bone marrow had been destroyed. The hope was that the study would show how a single blood-making cell could grow into millions of cells, including, perhaps, cells in other tissues of the body.

Instead, said Amy J. Wagers, first author of the study appearing this week in the journal Science, the group found that the blood stem cells replenished the bone marrow but made almost no other types of tissue cells. Wagers said "the study strongly suggests that blood stem cells make only one thing -- blood. Making skin, neurons, muscle, or liver cells, as some researchers have reported from such stem cells, is an extremely rare event that probably would not be useful in the treatment of disease," she said. "We only had one neuron out of millions of cells," said Wagers. "With the liver, the frequency was only 1 in 70,000. It can happen, but it is not robust."

The study is part of a new field of study directed toward regenerative medicine, which would cure or control disease by replacing flawed or worn-out cells with new cells grown from stem cells. Experts believe stem cells eventually may be cultured into new tissue that would be used to replace or repair ailing or diseased organs.

Researchers in many labs are studying two basic types of stem cells. Somatic, or adult, stem cells come from mature tissue. Embryonic stem cells come from embryos that have been allowed to grow to a certain point and then killed to extract the cells.

The Bush administration has put in place strict guidelines controlling the use of federal dollars for embryonic stem cell research, while putting no such restrictions on adult stem-cell studies. Some officials have argued that embryonic stem-cell studies are not needed because of growing evidence that adult stem cells, when properly cultured, can grow into other tissue cells for medical treatment But the work of Wagers and others suggest that adult stem cells offer only an uncertain promise of ever being medically useful. "What our study shows is that the most robust and reproducible production of multiple tissues from a single cell comes from the embryonic stem cells and not from adult blood stem cells," Wagers said.

Other stem cell researchers, however, say the issue is far from settled. Dr. Dennis A. Steindler, a stem-cell researcher at the University of Florida, said the "jury is still out" on which type of stem cell will be the most medically useful. "There is still a great deal to learn about the possible use of adult stem cells for therapeutics," he said. "The field of regenerative medicine is just beginning. We have a lot of experiments we need to do to figure out the way that stem cells can be used to cure human diseases." He said most experts believe that both adult and embryonic stem cell research should be continued vigorously, because it is possible that both types of cells eventually will find a place in medicine.

Dr. Michael D. West, CEO, Advanced Cell Technology in Worcester, MA, said the Stanford study is part of a growing awareness among researchers that "stem cells from the bone marrow will not be a practical source for many cell types needed to treat disease."

Dr. Catherine Verfaillie, Director of the University of Minnesota Stem Cell Institute, said her lab "has grown many different types of tissue cells from bone marrow stem cells." She said "the Stanford study used a different bone marrow stem cell and processed it differently. As a result, she said the two studies really can't be compared."