April 17, 2003
Putting bone-marrow stem cells to work in muscles
Dr. Helen Blau’s early scientific work focused on a lowly worm, a silkworm moth to be exact. But like the caterpillar in Lewis Caroll’s “Alice in Wonderland,” the worm pointed in a more interesting direction. Blau’s Ph.D. work on the biology of silkworm secretion led her to examine cell plasticity in mammals — whether or not adult stem cells present in bone marrow can function in other parts of the body in response to injury caused by trauma or disease.
Blau, the Donald E. and Delia B. Baxter professor of pharmacology and director of the endowed Baxter Laboratory in Genetic Pharmacology at Stanford University School of Medicine, has demonstrated that adult stem cells within bone marrow are dynamic and may have therapeutic applications restoring or replacing brain and muscle cells damaged by Parkinson’s disease, stroke, other central nervous system diseases, and muscular dystrophies.
“We’ve found that bone marrow-derived stem cells in adults have the capacity to contribute to diverse tissues, particularly brain and muscle,” says Blau. These cells may be precursors to tissue-specific stem cells in adults, such as healthy stem cells in blood or satellite cells in muscle.
Blau and colleagues studied brain-cell samples from women who had received bone marrow transplants from male donors. The donor male transplant cells had Y chromosomes. The researchers marked the healthy male donor Y chromosomes with a green fluorescent protein to identify them as different from the women’s cells. Stains of autopsy cells from the women revealed green fluorescent Y chromosomes in blood cells but also, surprisingly, in Purkinje cells in the brain.
In humans, Purkinje cells in the brain control balance and movement and are only known to develop before birth. According to Blau, the presence of green fluorescent markers of male bone marrow cells in these brain cells indicates something new.
“We think these adult stem cells, the green cells, are a repair squad that respond to damage,” says Blau.
To track the path of the hypothesized stem-cell repair squad, Blau and her team irradiated bone marrow cells in mice and then transplanted healthy bone marrow cells. Again the researchers marked healthy stem cells with a green fluorescent protein. Once injected into the irradiated mice, the green cells took over and made more green cells — and rescued the mouse from death. In the irradiated mouse, Blau said, the green stem cells were working as muscle fiber cells in more than 20 muscle groups.
“We have proof of this in muscle. When we exercised the irradiated mouse—exercise being a form of damage—the green cells later appeared in the muscles. The green cells derived from marrow could self-renew. We reproduced them as colonies of muscle cells in culture.”
Blau and her team have also found a significant difference in the abilities of different muscle groups to take up the green cells.
“Some muscles did better than others, in response to the same conditions,” said Blau. “Very active muscle cells had more green cells.”
After comparing the muscle fibers Blau’s group can get a 5 percent muscle fiber re-uptake, where there was only .1 percent or less re-uptake before.
“The Holy Grail would be having the ability to deliver a drug that recruits the stem cells where we need them and have an optimized re-uptake,” says Blau.
Blau presents the Annual Science in Medicine Lecture, “Stem Cells Within Adult Bone Marrow: Role in Tissue Repair,” at noon, Thursday, April 24, in Hogness Auditorium, room A-420, Health Sciences Center.
Blau received a Ph.D. degree in biology from Harvard University. She completed a postdoctoral fellowship in medical genetics, biochemistry and biophysics at the University of California, San Francisco, and joined the Stanford faculty in 1978. Among numerous awards, Blau received the Women in Cell Biology Senior Career Recognition Award from the American Society of Cell Biology in 1992, and the 1999 Excellence in Science award from the Federation of American Societies for Experimental Biology. She has served as president of the Society for Developmental Biology. Blau is the recipient of a National Institutes of Health MERIT award and is an elected member of the American Academy of Arts and Sciences and the Institute of Medicine of the National Academy of Sciences.