In Depth
Rebuilding bone
Adult stem cells hold promise for skeletal repair.
Hear the term "stem cells" and it's likely you think of human embryos and high-profile controversy. Fact is, stem-cell therapy has been quietly practiced for some 40 years.
Hematopoietic stem cells, the precursors of blood cells, were identified in bone marrow back in the 1960s. Since their discovery, bone-marrow transplants—the destruction of diseased marrow and "re-seeding" with healthy stem cells—have been used in the treatment of leukemia, lymphoma, and other blood disorders.
Distribution of mesenchymal stem cells in a baby mouse 7 days after the cells were injected into the mouse's bloodstream. By tagging the cells with green fluorescent protein, Niyibizi shows they find their way into many tissues and organs. Courtesy Christopher Niyibizi
More recently, however, researchers have found stem cells in many other types of mature tissue, including brain, blood vessel, skin, fat, muscle, and liver—and the list continues to grow. Their job, says Christopher Niyibizi, is regeneration and repair. "In the case of tissue damage or injury, they kick on and begin producing healthy new cells."
At first, these "adult" stem cells were not considered very promising for cell-based therapies. They are usually found in very small quantities, which makes them difficult to collect and purify. Unlike embryonic stem cells, they lose their potential if maintained in culture for long periods of time. Most importantly, adult stem cells are far less "plastic" than their better-known counterparts: Where embryonic stem cells have an unrestricted capacity for self-renewal and the potential to differentiate into any type of adult cell, adult stem cells are much more limited in the types of cells they can become.
On the other hand, some say, adult stem cells could bypass the immune-system challenges that are likely with transplant from donor to patient. Nor do adult cells raise the ethical concerns that arise from using human embryonic stem cells.
Spurred in part by those concerns, researchers are looking more closely at adult stem cells. Recent findings suggest that these cells may be more flexible, and therefore more useful, than previously thought.
Bone marrow extract
Christopher Niyibizi
Niyibizi, an associate professor of orthopaedics and rehabilitation and biochemistry and molecular biology at the Penn State College of Medicine, is interested in their potential for regenerating bone. He works with mesenchymal stem cells taken from bone marrow and fat, which have the capacity to become bone, fat, or cartilage. "You can direct what they become, by adding specific growth factors," he explains.
A dramatic example of the short-term promise of these cells made headlines late in 2004, when German surgeons used them to repair a large hole in the skull of a 7-year-old girl who had been severely injured in an accident. Extracted from fat taken from the girl's buttocks, the cells were mixed with a small amount of powdered bone from her pelvis—"as a scaffold," Niyibizi says—and placed on the 19-square-inch area of exposed brain. Within several weeks, the German team reported, the hole was filled with new-grown bone.
It was apparently the first time stem cells had been used to grow bone in a human. But because the patient was human, it was impossible to prove that it was actually the stem cells that had done the work. To get a better view, literally, of what these cells do in the body requires recourse to animal models. Niyibizi uses one such model with mice, taking advantage of a commonly used biological marker known as green fluorescent protein.
"We infect the cells with a virus we have engineered to contain the gene that makes this protein," he explains. "Once it enters the body, the infected cell makes the protein, which causes the cell to glow green when observed under a fluorescent microscope. In this way, it can be tracked after it is injected into the body."
In a recent experiment, Niyibizi injected these tinted cells directly into the bone cavities of mice afflicted with brittle bone disease, a congenital skeletal disorder. On the desktop computer screen in his office at the Hershey Medical Center he flashes before-and-after images. In the first, the dark outline of a mouse's femur is paper-thin, giving the knobby head of the bone a hollowed-out appearance. A second cross-section taken four weeks later shows the same cavity filled with a mix of gray and green tinted shadow. "You can see here that there was successful engraftment," Niyibizi says. "The stem cells were accepted and have started producing bone.
"We still need to do strength and structural tests to see if this bone is actually normal," he stresses. "But if it is, this could be important for treating bone loss in the elderly, especially osteoporosis."
Next page: "A whole new skeleton..."
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