Five patients who lost large amounts of muscle in their legs were able to grow it back. With the help of pig bladder lining, scientists coaxed stem cells into becoming muscle cells in the patients’ bodies.
Muscle can regenerate after an injury, but not if large amounts are destroyed -- such as with military wounds and traumatic accidents. Treatments are limited for these extreme cases of muscle loss, where scar tissue formed to fill in the gap. Stem cells have been shown to work, and these therapies usually follow a similar pattern: take stem cells from the patient, help them develop into the cells of choice, then inject them back.
Now, a University of Pittsburgh team led by Stephen Badylak developed a different kind of stem cell treatment that doesn’t involve taking out and adding back stem cells; rather, the stem cells stay in the body. The technique relies on extracellular matrix (ECM) -- the lattice of protein molecules that add structure to living tissue. Once implanted in the body, ECM recruits stem cells to the injury site, where they’re coaxed into becoming muscle cells.
To create thin sheets of biological scaffolding, the team stripped the lining of pig bladders of all their cells -- except for collagen, sugars, and structural proteins. Quilts of compressed extracellular matrix sheets are commercially available and commonly used as support to treat herniated abdominal walls and help with breast reconstruction.
After the method was successful in rodents with injured hind limbs, the team moved on to humans who have lost between 58 and 90 percent of their leg muscle. These five men had exhausted their other options, including multiple surgeries. Three were in the military (two were injured during blasts from improvised explosive devices), and the other two were injured in skiing accidents.
The patients had all completed a customized, 12 to 16-week physical therapy program. After they plateaued, and no longer showed signs of improvement for two weeks, the men received the ECM implants. First, the researchers had to surgically remove the scar tissue, and then they sutured in the scaffolding material. After a day or two, each patient returned to their physical therapy regimen for another five to 23 weeks.
As the matrix scaffold degrades, it acts as a homing device, sending out chemicals to recruit stem cells and other progenitor cells to the injury site. Post-treatment physical therapy is crucial because it triggers signals that direct stem cells toward becoming muscle cells, rather than some other kind of cell like fat or cartilage. That’s because mechanical forces tell the recruited stem cells to develop into properly aligned muscle tissue, Badylak explains in a teleconference. "The cells get the idea to say: 'OK. I get it. I'm supposed to line up this way. I'm supposed to be the type of a cell that can bear weight, or contract,'" he adds. "If that doesn't happen when they get there, and they don't get those signals, they can turn into anything else."
When the cells do mature into muscle cells, they help develop healthy, brand new tissue. In each patient, muscle regrew and were partially restored to their normal appearance. Half a year after surgery, MRI and CT imaging, as well as biopsies, revealed dense tissue at the implantation site. The procedure was considered a success if they improved at least 25 percent in day-to-day activities like walking, taking the stairs, or getting out of a chair. Three of them achieved this, though they all reported an improved quality of life.
The work was published in Science Translational Medicine this week.
Image: Elke Brown and Fabrisia Ambrosio