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Releases Packard
Children's News
Children's Fund
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A Perfect Place to HealBY MEREDITH ALEXANDER KUNZ WINTER 2006 -- A child born with a cleft lip or palate may endure as many as nine surgeries throughout childhood to repair the defect. To reduce the number of surgeries dramatically -- and perhaps eliminate the need for them altogether -- physician-scientists at Lucile Packard Children's Hospital are seeking to understand how the disorder develops in the womb.
Harnessing knowledge from developmental and molecular biology, genetics, and regenerative medicine, researchers from Stanford’s Institute for Stem Cell Biology and Regenerative Medicine are collaborating to find solutions to clefting, the most common birth defect after heart malformations. Led by Michael Longaker, MD, FACS, deputy director of the Institute and director of Children's Surgical Research at Packard Children's Hospital, the team is conducting research that could help the one in 700 babies born worldwide with a cleft lip and/or palate. Healing in the WombOne novel approach to cleft palate repair is examining how babies heal wounds while they are still in utero. Peter Lorenz, MD, professor of plastic surgery, says that healing in the womb would eliminate surgical scarring and its "ripple effect" of other injuries for children with cleft palate. Besides affecting a child's appearance, scarring also inhibits facial growth, as well as speech function and tooth development.
"If we could get rid of the scarring, we could reduce the problems in those other areas," says Lorenz. To do so, he is examining the seemingly miraculous wound-healing abilities of the fetus. Unlike children or adults, fetuses who suffer skin injuries in the womb heal perfectly -- their tissues regenerate without a trace of injury. Lorenz has researched the possibility of correcting cleft lip and palate by performing surgery in utero. Through animal models, he and Longaker have found that wounds that are repaired early enough in gestation will heal without scars. If scientists could understand the cellular and molecular mechanisms behind fetal healing, "we would have a blueprint for ideal repair," Lorenz explains. Researchers could then "apply that biology to treat children's cleft palates," says Lorenz, who is using microarrays to gather information on the roles of genes and stem cells in fetal skin repair. Lorenz hopes this work will lead to a day when only one surgery will be required to correct a cleft lip or cleft palate. "There would be no need for orthodontic treatment or for speech therapy; we could reduce the need for dental intervention and for future facial bone surgery," he says. Looking for GenesAnother Stanford scientist, Jill Helms, DDS, PhD, associate professor of surgery, is tackling cleft repair by uncovering the genetic tools that build facial structure. "We are trying to understand how the face is put together, and what disrupts it. If we understand how things go wrong, maybe we will have the chance to prevent clefting," she explains.
The molecular "toolbox" used to construct a face is similar throughout the animal kingdom, Helms says, which is why facial development in small animals, such as birds and mice, can tell us a great deal about human face formation. Researchers in Helms' lab, for example, study the different stages of facial development by making a tiny hole in a fertilized egg and observing a bird embryo as it develops. Using a mouse model, scientists also are able to knock out certain genes to see which might alter the way the face takes shape. Though it is the most common facial birth defect, clefting is hard to predict because most patients have no family history of it. "This means that multiple genes must be acting in concert with each other to lead to the defect," Helms says.
Roeland Nusse, PhD, a Stanford developmental biologist and Howard Hughes investigator whose lab is studying genes that control embryonic development, is helping Helms narrow down which genes play a role in facial development. Finding genes responsible for clefting in humans and explaining how these genes disrupt normal development could lead to insights into genetic therapies or drugs that could repair or mitigate clefting in babies before they are born. But until a time comes when cleft lip and palate can be cured, whether in utero or by genetic intervention, advances in surgery and tissue regeneration fostered by Longaker and his team are of enormous value to the thousands of patients who suffer from this defect. Together, these Packard researchers are leading the way in both the repair and prevention of clefting.
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