Researchers regrow lost muscle in injured patients with novel stem-cell technique

Sheryl Ubelacker, The Canadian Press

TORONTO - Researchers have been able to rebuild severely damaged leg muscles in a small number of patients by implanting a pig bladder "scaffold" that draws the body's own stem cells to the site and coaxes them into becoming new muscle cells.

The experimental technique was used on five men who had lost between 60 per cent and 90 per cent of muscle in either their thigh or below the knee, leaving them unable to walk normally or perform other actions that require healthy leg muscles.

Three of the patients were in the military: two had combat-related blast injuries, while the third had exercise-induced muscle damage. The other two were civilians who had been seriously hurt in skiing accidents. All had undergone multiple surgeries and months, even years, of rehab.

"Frankly, most of these patients have been through hell," said principal investigator Dr. Stephen Badylak, deputy director of the McGowan Institute for Regenerative Medicine at the University of Pittsburgh.

"The things that you and I take for granted — getting out of a chair, taking steps, stepping off a curb, getting out of a car — these are the types of deficits that these individuals had," Badylak told a media briefing about the study published online Wednesday in the journal Science Translational Medicine.

"These are young individuals," he said of the patients, who are in their 20s and 30s. "These are guys who have their lives ahead of them and they were really struggling. In fact, one or two of the patients even considered amputation at one point because they'd just been through so much."

In all five men, the stem cell therapy caused muscle to regrow, partially restoring normal appearance and improving their ability to walk and otherwise function, following an intense rehabilitation program.

Stem cells, which can differentiate into virtually any tissue in the body, have been shown to help damaged tissue regenerate. But in most cases, researchers isolate stem cells from the body, grow them into a particular cell type in the lab and then inject them back into patients.

Badylak and a team of researchers took a different approach: they used what amounts to the shell of a pig bladder that had been stripped of biologically active cells — called an extracellular matrix — as a scaffold on which stem cells could grow.

But the matrix not only acts as a framework; as it begins degrading, it sends out chemical signals that conscript stem cells to the area, where they are enticed into becoming functioning muscle cells.

"What we think ... is that the degradation products of these scaffolds are kind of homing beacons that recruit these cells ... and allow them to participate in the remodelling of the scaffold," said co-lead author Brian Sicari, a researcher at the university.

Prior to having the implant surgery, each patient had completed an intense 12- to 16-week physical therapy program customized to deal with their individual functional deficits. The rehab program continued until they reached a plateau and were unable to achieve any more improvement.

Following the implant, the patients were put back on their rehab regimen for another five to twenty-three weeks and success was determined by their ability to improve at least 25 per cent above their pre-operative maximum ability in day-to-day activities.

The researchers say this post-treatment physical therapy, which began within 48 hours of the implant surgery, is critical to treatment success because it appears to trigger signals that direct stem cells towards becoming muscle cells, rather than some other kind of cell.

"This is a wonderful example of a multidisciplinary team coming together to move technology from the bench to the bedside," said co-lead investigator Dr. Peter Rubin, head of plastic surgery at the University of Pittsburgh School of Medicine.

Injuries that destroy chunks of muscle can occur among military personnel exposed to explosions during combat, but also among civilians involved in industrial, motor-vehicle or sports-related accidents, said Rubin.

Treatment options are limited because of the large volume of muscle lost and the build-up of scar tissue, which can painfully impede movement.

"While the number of patients (in the study) was small, we were very encouraged by the data and we were seeing very dramatic improvements in quality of life for some of our patients," he said.

Badylak noted that treating patients with fresh wounds — for example, a soldier hurt in combat — might make the technique even more effective, although that would need to be proven with further research.

The same would be true for using the technique to grow new heart muscle after a heart attack, for instance.

"It would remain to be shown because every anatomic location is different," he said, noting that some areas of the body respond better than others to stem cell therapy.

"So when you now start moving to other issues like heart tissue, or somewhere in the gastrointestinal tract or reproductive tract, even though the concepts are the same ... the outcomes will remain to be shown through the type of study we just did here."

The researchers hope their work, partly funded with a $3-million grant from the U.S. military, will be duplicated by scientists at other institutions.

"The approach that we've taken is intended to be the type of approach that can be utilized literally anywhere that a good surgeon's available," said Badylak. "This is not intended to be something that's specific to university settings, certainly not to the University of Pittsburgh."

As long as such health-care providers understand the science behind the procedure, they should be able to get the same results in their own patients using this technique, he concluded.

"It's nice to conduct a study where we can show pretty pictures of stem cells and all of that, but if it doesn't make a difference for the patient at the end of the day, it's nothing other than a study, in my opinion," Badylak said.

"So I think one of the major outcome measures of this study that's of note is that these patients got better."

Follow @SherylUbelacker on Twitter

© The Canadian Press , 2014