Laboratory-engineered skeletal muscle is a potential therapy for replacing diseased or damaged muscle tissue. This computer-controlled system is designed to build properly organized muscle tissue in the lab. To do this, muscle cells are attached to strands of a natural material and are then subjected to cyclic stretching (“exercise”) in a device designed to simulate the conditions of the human body. The pre-conditioning allows the cells to align in one direction, fuse to form muscle bundles, and function like normal muscle. Credit: Wake Forest Baptist Medical Center |
New
research shows that exercise is a key step in building a muscle-like
implant in the lab with the potential to repair muscle damage from
injury or disease. In mice, these implants successfully prompt the
regeneration and repair of damaged or lost muscle tissue, resulting in
significant functional improvement.
“While
the body has a capacity to repair small defects in skeletal muscle, the
only option for larger defects is to surgically move muscle from one
part of the body to another. This is like robbing Peter to pay Paul,”
said George Christ, Ph.D., a professor at Wake Forest Baptist Medical
Center’s Institute for Regenerative Medicine. “Rather than moving
existing muscle, our aim is to help the body grow new muscle.”
In the current issue of Tissue Engineering Part A,
Christ and team build on their prior work and report their second round
of experiments showing that placing cells derived from muscle tissue on
a strip of biocompatible material—and then “exercising” the strip in
the lab—results in a muscle-like implant that can prompt muscle
regeneration and significant functional recovery. The researchers hope
the treatment can one day help patients with muscle defects ranging from
cleft lip and palate to those caused by traumatic injuries or surgery.
For
the study, small samples of muscle tissue from rats and mice were
processed to extract cells, which were then multiplied in the lab. The
cells, at a rate of 1 million per square centimeter, were placed onto
strips of a natural biological material. The material, derived from pig
bladder with all cells removed, is known to be compatible with the body.
Next,
the strips were placed in a computer-controlled device that slowly
expands and contracts—essentially “educating” the implants on how to
perform in the body. This cyclic stretching and relaxation occurred
three times per minute for the first five minutes of each hour for about
a week. In the current study, the scientists tried several different
protocols, such as adding more cells to the strips during the exercise
process.
The
next step was implanting the strips in mice with about half of a large
muscle in the back (latissimus dorsi) removed to create functional
impairment. While the strips are “muscle-like” at the time of
implantation, they are not yet functional. Implantation in the
body—sometimes referred to as “nature’s incubator”—prompts further
development.
The
goal of the project was to speed up the body’s natural recovery process
as well as prompt the development of new muscle tissue. The scientists
compared four groups of mice. One group received no surgical repair. The
other groups received implants prepared in one of three ways: one was
not exercised before implantation, one was exercised for five to seven
days, and one had extra cells added midway through the exercise process.
The results showed that exercising the implants made a significant
difference in both muscle development and function.
“The
implant that wasn’t exercised, or pre-conditioned, was able to
accelerate the repair process, but recovery then stopped,” said Christ.
“On the other hand, when you exercise the implant, there is a more
prolonged and extensive functional recovery. Through exercising the
implant, you can increase both the rate and the magnitude of the
recovery.”
A
variety of laboratory tests were used to measure results. A test of
muscle force at two months, for example, showed that animals who
received the implants with extra cells added had a threefold increase in
absolute force compared to animals whose muscle damage was not
repaired. The force-producing capacity of muscle is what determines the
ability to perform everyday tasks.
“If
these same results were repeated in humans, the recovery in function
would clearly be considered significant,” said Christ. “Within two
months after implantation, the force generated by the repaired muscle is
70% that of native tissue, compared to 30% in animals that
didn’t receive repair.”
The
results also showed that new muscle tissue developed both in the
implant, as well as in the area where the implant and native tissue met,
suggesting that the implant works by accelerating the body’s natural
healing response, as well as by prompting the growth of new muscle
tissue.
The
researchers hope to evaluate the treatment in patients who need
additional surgery for cleft lip and palate, a relatively common birth
defect where there is a gap in muscle tissue required for normal facial
development. These children commonly undergo multiple surgeries that
involve moving muscle from one location to another or stretching
existing muscle tissue to cover the tissue gap. The implant used in the
current research is almost exactly the size required for these
surgeries.
“As
a surgeon I am excited about the advances in tissue-engineered muscle
repair, which have been very promising and exciting potential in the
surgical correction of both functional and cosmetic deformities in cleft
lip and cleft palate” said Phillip N. Freeman, M.D., D.M.D., associate
professor of Oral and Maxillofacial Surgery at the University of Texas
Health Science Center at Houston. “Current technology does not address
the inadequate muscle volume or function that is necessary for complete
correction in 20 to 30% of cases. With this innovative technology there
is the potential to make significant advances in more complete
corrections of cleft lip and cleft palate patients.”
The
technology was originally developed under the Armed Forces Institute of
Regenerative Medicine (AFIRM) with funding from the Department of
Defense and the National Institutes of Health. The sponsor of the
current research was the Telemedicine & Advanced Technology Research
Center. A longer-term goal is to use the implant—in combination with
other tissue-engineered implants and technologies being developed as
part of AFIRM—to treat the severe head and facial injuries sustained by
military personnel. For example, AFIRM-sponsored projects under way to
engineer bone, skin and nerve may one day be combined to make a
“composite” tissue.