Mar. 31, 2010 A Columbia scientist has become the first to grow a complex, full-size bone from human adult stem cells.
Gordana Vunjak-Novakovic, a professor of biomedical engineering at the Fu Foundation School of Engineering and Applied Science, reports that her team grew a temporomandibular joint (TMJ) from stem cells derived from bone marrow. Her work is reported in the online Early Edition of the journal Proceedings of the National Academy of Sciences this month.
"The TMJ has been widely studied as a tissue-engineering model because it cannot be generated easily, if at all, by current methods," says Vunjak-Novakovic, whose co-authors include Warren L. Grayson, then a post-doctoral student in her lab and now an assistant professor at Johns Hopkins University. Around 25 percent of the population suffers from TMJ disorders -- including those who suffer from cancer, birth defects, trauma and arthritis -- which can cause joint deterioration. Because the TMJ is such a complex structure, it is not easily grafted from other bones in a patient's body. "The availability of personalized bone grafts engineered from the patient's own stem cells would revolutionize the way we currently treat these defects," she says.
Current methods of treating traumatic injury to the jaw include taking a bone from the patient's leg or hip to replace the missing bone. "Wouldn't it be wonderful if we could get the patient's own stem cells and grow a new jaw?" says Dr. June Wu, a craniofacial surgeon at Columbia University Medical Center who advised Vunjak-Novakovic on her research.
Vunjak-Novakovic's technique for turning stem cells into bone was inspired by the body's natural bone-building process. Her team started by analyzing digital images of a patient's jawbone in order to build a scaffold into the precise shape of a TMJ joint. The scaffold itself was made from human bone stripped of living cells. The team then seeded the scaffold with bone marrow stem cells and placed it into a custom-designed bioreactor. The reactor, filled with culture medium, nourished and physically stimulated the cells to form bone. "Bone tissue is metabolically very active," she says. Bone tissue develops best when it is bathed in fluid flowing around it. Vunjak-Novakovic and the team looked into the exact flow rates one needs for optimal effects. After five weeks, they had a four-centimeter-high jawbone that was the precise size and shape of a human TMJ.
The technique can be applied to other bones in the head and neck, including skull bones and cheek bones, which are similarly difficult to reconstruct, but Vunjak-Novakovic started with the TMJ because, "We thought this would be the most rigorous test of our technique," she said. "If you can make this, you can make any shape."
Her team's next step is to develop a way to connect the bone graft to a patient's blood supply to ensure that the graft grows with the person's body. "Our bones change, and these biological grafts would change with us," says Vunjak-Novakovic.
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- W. L. Grayson, M. Frohlich, K. Yeager, S. Bhumiratana, M. E. Chan, C. Cannizzaro, L. Q. Wan, X. S. Liu, X. E. Guo, G. Vunjak-Novakovic. Regenerative Medicine Special Feature: Engineering anatomically shaped human bone grafts. Proceedings of the National Academy of Sciences, 2010; 107 (8): 3299-3304 DOI: 10.1073/pnas.0905439106
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