Regenerating Small Human Muscles Holds Potential for Dramatic Improvements in Craniofacial Reconstruction
UCSF News reports on research in the UCSF Program in Craniofacial Biology using stem cells from patients with craniofacial deformities to better understand how these design flaws occur in fetal development. Among other research projects, the article reported on the work of Jason H. Pomerantz, M.D., Surgical Director of the UCSF Craniofacial Center, who is using stem cells and regenerative techniques to reconstruct tiny muscles in the face using a humanized organ in a mouse model.
Together, these members of the UC San Francisco faculty are cultivating organs of the craniofacial complex – the skull and face – which too often go terribly wrong during fetal development. Deformities of these bones or soft tissues, the most common of birth defects, can cut life short by blocking the airway or circulation. Or they can disfigure a face so profoundly that a child struggles to see, hear, or talk. Perhaps most painful of all, such deformities render children physically other, potentially leading to a lifetime of corrective surgeries and social isolation.
Jason H. Pomerantz, M.D., a plastic surgeon, falls into the regeneration camp. His clinical work is typified by a recent eight-hour operation on a 17-year-old boy with Crouzon syndrome, a severely disfiguring condition affecting every organ in the craniofacial structure – muscle, bone, and skin. “My patient is excited for the outcome, but not about the process,” says Pomerantz, surgical director of the UCSF Craniofacial Center. For three months, the patient will wear a large metal frame on his head with wires that will pull the bones in his face forward. Prior to the surgery, the boy’s face was nearly concave, collapsed inward at the nose.
Yet bone is not all Pomerantz needs to work with to restructure a face. The subtle bends, creases, and curves of expression that make a face one’s own are the work of tiny muscles. “Right now we can move a big muscle – say, from the thigh to the face – so that people can smile,” he says. “But we can’t reconstruct the fine ones that enable people to move their eyebrows up or move the eyeballs around. That requires little muscles. This is where we can make headway with stem cell biology.
“We have actually made a humanized organ in an animal,” he continues, pointing to a picture of a mouse on his wall. Pomerantz is now considering incubating small human muscles in animals for use in his patients’ faces. In a recent project, he inserted stem cells from human muscles into a mouse whose own muscle stem cells had been incapacitated. He then perturbed the muscle to stimulate regeneration. As the muscle healed, the cells created new muscle tissue, which the mouse’s nerves innervated to make a functioning muscle. It’s exactly the size of the muscles Pomerantz needs for full articulation of expression and function in a human face or hand.
About the Pomerantz Lab
Led by Jason H. Pomerantz, M.D., Associate Professor of Surgery and Surgical Director of the UCSF Craniofacial Center, the Pomerantz Lab studies basic and translational aspects of tissue regeneration. With foundations in muscle and cancer biology, the lab investigates regenerative mechanisms including stem cell development and de-differentiation. Using model organisms such as zebrafish and mice, and extending discoveries to human cells and tissues, the lab hopes to gain fundamental insight that can be translated into clinical advances, notably solving the structural and reconstructive problems of the limbs, face, and head, whether congenital or acquired.