- By tapping into the immune system, researchers have developed a way to
help adult muscle tissue heal by regenerating in the lab, according to a
study of mice.
Biomedical engineers at Duke University believe engineered tissue grafts
can better survive in future cell therapy applications, offering ways
to treat degenerative muscle diseases. The findings were published
Monday in the journal Nature Biomedical Engineering.
Lab-made adult muscle tissues do not have the same regenerative
potential as newborn tissue, but many degenerative muscle diseases do
not appear until adulthood.
"I spent a year exploring methods to engineer muscle tissues from adult
rat samples that would self-heal after injury," researcher Dr. Mark
Juhas, a former Duke doctoral student, said in a press release. "Adding
various drugs and growth factors known to help muscle repair had little
effect, so I started to consider adding a supporting cell population
that could react to injury and stimulate muscle regeneration. That's how
I came up with macrophages, immune cells required for muscle's ability
to self-repair in our bodies."
Juhas is part of the lab of Nenad Bursac, a professor of biomedical
engineering at Duke who debuted the world's first self-healing,
lab-grown skeletal muscle in 2014. The muscle healed itself inside the
laboratory and an animal.
They took samples of muscle from rats just two days old, removed the
cells and "planted" them into a lab-made environment perfectly tailored
to help them grow.
Niches for muscle stem cells, known as satellite cells, activated upon injury and aided the regeneration process.
Macrophages, which are translated from Greek as "big eaters," are white
blood cells in the body's immune system that engulf and digest cellular
debris, pathogens and anything else they don't think should be hanging
around. In addition they secrete factors that support tissue survival
and repair.
After a muscle injury, a class of macrophages increases inflammation and
stimulates other parts of the immune system. One of the cells recruited
is a second kind of macrophage, dubbed M2, that decreases inflammation
and encourages tissue repair.
"When we damaged the adult-derived engineered muscle with a toxin, we
saw no functional recovery and muscle fibers would not build back,"
Bursac said. "But after we added the macrophages in the muscle, we had a
wow moment. The muscle grew back over 15 days and contracted almost
like it did before injury. It was really remarkable."
The researchers believe the macrophages act to protect damaged muscle
cells from apoptosis, which is the process of programmed cell death.
Although newborn muscle cells naturally resist stopping the process,
adult muscle cells need the macrophages. These surviving muscle fibers
help muscle stem cells latch onto them and perform their regenerative
duties.
"We believe that the macrophages in our engineered muscle system may
behave more like the muscle-resident macrophages people are born with,"
Bursac said. "We are currently working to understand if this is indeed
the case. One could then envision 'training' macrophages to be better
healers in a system like ours or augmenting them by genetic
modifications and then implanting them into damaged sites in patients."
This means that adult tissues can be as effective as fetal and newborn tissues in healing.
"Building a platform to test these results in engineered human tissues
is a clear next step," Bursac said. "We hope that our approach of
supplementing lab-grown muscles with immune system cells will prove to
be a general strategy to augment survival and function of other
lab-grown tissues in future regeneration therapies."
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