Researchers have found the first evidence that adult bone marrow-derived cells can differentiate in vitro and in vivo into cells of all three embryonic germ layers (endoderm, ectoderm and mesoderm) in a similar manner as embryonic stem cells (ES cells). (Nature, 20-Jun-2002)
University of Minnesota
Researchers at the University of Minnesota Stem Cell Institute (SCI) have found the first evidence that adult bone marrow-derived cells can differentiate in vitro and in vivo into cells of all three embryonic germ layers (endoderm, ectoderm and mesoderm) in similar manner as embryonic stem cells (ES cells). SCI Director Catherine Verfaillie, M.D., and her colleagues call these cells multipotent adult progenitor cells (MAPCs). The results of the research are published by Nature and will be available online Thursday, June 20, 2002, at http://www.nature.com/nature. The results will be presented at 9:30 a.m. the same day at a press conference in Minnesota. Verfaillie, the lead researcher, reports that cells grown from adult mouse and rat bone marrow can be cultured without aging and with active telomerase, an enzyme found in embryonic stem cells that prevents aging.
In subsequent studies, Verfaillie's lab showed that single MAPCs can contribute to most, if not all, tissues of mice after they have been injected into the blastocyst of a mouse. The result is a chimerical animal. "This occurs with one out of every three cells, and contribution is to all tissues of the mouse," said Verfaillie. "Some of the animals are 40 percent derived from the bone marrow stem cells, suggesting that the cells contribute functionally to a number of organs. Again, this is similar to what one would expect of ES cells.
"In contrast to ES cells, when we inject the bone marrow stem cells into recipient animals, the bone marrow stem cells do not form teratomas [tumors containing many different tissue types], but respond to local cues and differentiate into blood cells as well as into epithelium of liver, gut, and lung."
In response to recent critics of the potential of adult stem cells, Verfaillie's research shows in vitro that a single cell differentiates into cells of the three germ layers, that they were euploid (correct number of chromosomes) and that they never co-cultured the bone marrow cells with endothelial, neuronal or liver cells. Therefore, the in vitro observation cannot be the result of fusion. Verfaillie also shows that the chimerism is balanced and that engraftment occurs without selectable pressure.
Verfaillie said she believes that adult stem cells may hold therapeutic promise, but cautioned that a large number of studies is still required to fully characterize the potential of MAPCs. Side by side comparison of adult and embryonic stem cells must be done to determine which stem cells, adult or embryonic, are most useful in treating a particular disease.
According to Verfaillie, adult stem cells, cultured under specific conditions,
may be suitable for treatment in vivo of genetic or degenerative disorders.
They appear able to respond to local cues in
the animal and differentiate appropriately without tumor formation and might therefore be used as undifferentiated cells. Alternatively, they could be pre-differentiated prior to transplantation, although that hypothesis still must be tested. Finally, they may be suitable for determination of pathways responsible for differentiation, or as a source of differentiated cells for toxicology studies.
In a separate paper, also published online this week, Ron McKay and colleagues at the National Institute of Neurological Disorders and Stroke in Bethesda, Md., show that mouse ES cells can be used in cell-replacement therapy in an animal model of Parkinson's disease. From cultured ES cells, the group generated a large supply of neurons that produce dopamine.When transplanted into the brains of rats with damaged dopamine neurons (modeling Parkinson's disease), the neurons functioned normally.
Furthermore, the rats treated with the new neurons showed signs of recovery in behavioral tests.
In addition to the publication, Nature will post a web focus on Thursday, June 20. It will include access to both papers and news coverage on recent stem cells news at http://www.nature.com/nature/stemcells.
The objective of the Stem Cell Institute is to further our understanding of the potential of stem cells to improve human and animal health. The SCI is a part of the University of Minnesota's Academic Health Center and is an interdisciplinary center with member faculty representing a diverse group of university schools, colleges and centers. For online information about the University of Minnesota's Stem Cell Institute, go to http://www1.umn.edu/stemcell.
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Catherine Verfaillie, M.D., director, University of Minnesota Stem Cell
Ron McKay, Ph.D., senior investigator, National Institute of Neurological Disorders and Stroke, Bethesda, Md.
Natalie De Witt, Ph.D., senior biological sciences editor, Nature
Sarah Youngerman, Academic Health Center, (612) 624-4604 pager: (612) 899-6687
Deane Morrison, University News Service, (612) 624-2346
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