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Researchers regrow lost muscle in patients with novel stem cell technique

muscleregrowth.jpgMay 1, 2014 — 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.


May 1, 2014
By Sheryl Ubelacker The Canadian Press

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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.”


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