Pitt team tricks body to grow new muscle

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Pittsburgh-based medical scientists have figured out how to grow new muscle in injured patients by using extracellular matrix derived from pig bladder.

Nicholas Clark, a 34-year-old electrical engineer from Youngwood, Westmoreland County, was one of the first to benefit from the experimental procedure, which represents the first time science has shown successful replacement of functional muscle in humans.

Mr. Clark was left with a chronic limp after a 2006 skiing injury involving a spiral fracture of the tibia and fibula in his lower left leg. It also left him without muscle in one of four muscle compartments in that leg, along with additional muscle loss.

After traditional surgery and extensive rehabilitation, he still had trouble with his stride, his balance and pushing off with his left foot, forcing him to use a cane or ankle-foot orthotic device.

But in February 2012, J. Peter Rubin, a UPMC surgeon and director of the University of Pittsburgh School of Medicine department of plastic surgery, performed the novel muscle-replacement surgery on Mr. Clark.

And it worked.

His leg hasn't returned to full function, Mr. Clark said, but he can walk almost normally with ability to push off with his left foot. He also has better balance on his left leg. He can play table tennis and ride a bicycle, which he had difficulty doing prior to the surgery.

"Knowing what I know, I would never hesitate to have this done," Mr. Clark said. "I know the viability of the surgery. If it's an option for someone, I would recommend they do it."

The team of researchers from the medical school and the McGowan Institute of Regenerative Medicine, jointly operated by Pitt and UPMC, announced success Wednesday in regenerating muscle volume in five patients, including Mr. Clark, all of whom had disabilities from severe muscle-loss injury, including battle wounds.

When a traumatic injury results in the loss of a large volume of muscle, the body usually can't respond sufficiently to replace it. Scar tissue also can impair strength and function.

But Stephen F. Badylak, deputy director of the McGowan Institute, Dr. Rubin and their research team used a quilt of extracellular matrix -- collagen-based scaffolding that remains after all cells are removed from pig bladder tissue -- as framework to generate new muscle.

The matrix, naturally containing growth factors, is surgically placed under tension in the area where muscle was lost. By its nature, the matrix attracts stem cells and other progenitor cells from neighboring muscle, which signal the stem cells to turn into muscle cells. The tension in the matrix also alerts the new cells that they must bear weight and be flexible.

Eventually the matrix degrades as stem cells convert to muscle cells, which proceed to signal development of nerves and blood vessels. The result is regeneration of the patient's own muscle.

The research was published Wednesday in the journal Science Translational Medicine. Ever since that study was completed, Dr. Badylak said, four other patients have successfully undergone the procedure to replace muscle volume and improve functionality.

"These are patients who can't walk anymore, can't get out of a car, can't get up and down from a chair, can't take steps without falling. Now we might have a way of helping them get better," Dr. Badylak said.

As occurred with Mr. Clark, patients experiencing the loss of muscle volume from injury traditionally undergo surgery followed by extensive rehabilitation. Typically, though, they fail to regain adequate function, especially when a large amount of muscle is missing.

In the study, three patients, one with a calf injury and two others with thigh injuries, had lost at least 25 percent of muscle volume in those areas, affecting foot control or hampering their ability to walk. The procedure allowed them to regenerate 25 percent to 50 percent of lost muscle, followed by up to 26 weeks of rehabilitation, beginning just 48 hours after surgery. Dr. Badylak said the return of a portion of total muscle volume is sufficient to restore functionality.

One patient with a thigh injury improved dramatically in a single-hop test with the other showing exponential improvement in a chair-lift test and single-leg squat test. Biopsies and scans revealed muscle growth.

Even though two other patients with lower-leg injuries failed to regain 25 percent of lost muscle volume, they experienced sufficient regrowth to restore functionality in the affected limb, said Dr. Badylak, who was one of the first to use organ matrices to regenerate tissue. Such matrices now serve as scaffolding to regenerate esophageal linings, ligaments and other body parts, with use in repairing skin ulcers and hernias.

The project was done under a $3 million grant from the U.S. Defense Department to develop new methods to repair battlefield wounds.

Dr. Badylak said the procedure is now available to anyone who successfully undergoes a screening process, which can take as little as three or four weeks after the initial call. The team also said it plans to teach other medical teams at other medical centers nationwide how to perform the procedure.

"This work represents an important step forward in our ability to repair tissues and improve function with materials derived from natural proteins," Dr. Rubin stated.

Mr. Clark said he remains skittish about trying to ski once again.

"But there is a significant difference for me," he said. "Once I had lost certain function, getting any back is certainly significant."

David Templeton: dtempleton@post-gazette.com or 412-263-1578 First Published April 30, 2014 2:02 PM

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