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Reprinted by permission of The Chronicle of the Horse. Visit www.chronofhorse.com to suscribe.
A-Cell Therapy Offers Renewed
Hope For Horses Incurring Tendon
And Ligament Injuries
It’s hard to imagine that cells from pig bladders could
be useful for healing injured horses—but, it’s true.
Heather Smith Thomas
“The beauty of A-cell
therapy is its simplicity; you merely reconstitute the product
from a little bottle and
put it in the horse’s leg,”
said Rick Mitchell DVM, of
Fairfield Equine Associates in
Newtown, Conn., a staunch
believer in the therapy.
This image almost sounds too good to be
true. But so far veterinarians who’ve been
using this therapy for the past few years to
treat injured ligaments and tendons have
found that A-cell is a bonafide therapy that
aids the horse’s own body in the healing
process.
“The mixture acts as a framework for
the horse’s own circulating stem cells to populate the site and become appropriate, func-
tional tissue as the area heals, rather
than scar tissue,” added Mitchell.
Like its close relative stem
cell therapy, A-cell therapy has
allowed veterinarians to add
another useful tool to their
belts to help sport horses return
to their activities after, for example, injuring a suspensory ligament or straining a tendon.
“The fiber patterns on tendons, at 60 days after treatment,
look similar to the fiber pattern ultrasounds
with stem cell therapy,” said Mitchell. “Stem
cell therapy works well, but this process works
just as well and doesn’t involve having to collect tissue to get the stem cells, augment them
and put them back into the horse. The A-cell
treatment is also less expensive. It’s not cheap,
but it’s a lot cheaper than stem cell therapy.”
Cooper Williams VMD, of Hampstead, Md.,
has been using ACell Vet Powder (UBM—uri-
nary bladder matrix) treatments for tendon
injuries in horses and is pleased with the
results.
The A-cell product, which is available in
powdered form and a sheeted material, is produced by a tissue engineering company by the
same name. ACell Inc. is based on many years
of tissue research performed by Dr. Stephen
Badylak.
“The research was based on the search
for the signals the body uses to initiate healing processes, in humans and animals. When
we have an injury, our body must first recognize that it’s injured; then it has to go
through a series of processes to deal with the
injury. We know there are signals—otherwise
the wound would just sit there,” said
Williams.
Williams said tissue engineering is a
new field, and there are three basic approaches
in use.
The gene-based approach, which includes
stem cells, is using cells that haven’t yet
differentiated into anything, to try and heal
tissues.
A second approach is the use of purified
growth factor. The thought behind growth factor is that these are important in turning certain processes on within the body. This is true,
but the one problem is you don’t have an on
and off switch.
The third approach is scaffold-based, and
this is what ACell Inc. has focused upon.
Dr. Cooper Williams has found A-cell
treatment works wonders for steeplechasers
who’ve injured tendons and ligaments.
(Douglas Lees Photo)
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“This approach uses the extra cellular
matrix that surrounds the cells,” said
Williams. “In tissues, there’s cellular material
and also the three-dimensional support structure
around
the
cells—the
gridwork that holds them in place. For a long
time, in biological research, people thought
this was a fairly inert area, and that most of
the important things happened inside the
cells. They thought the three-dimensional
structure outside the cells was mainly just for
support.”
But as researchers explored what directs
the body—the signals the body uses to talk to
itself—they realized that the extra-cellular
matrix is actually a virtual information highway, and an important one at that.
The body uses this matrix area to “talk” to
itself. Otherwise, an injury wouldn’t heal,
because the rest of the body wouldn’t
know where it was. There are many substances that exist in that matrix, including
growth factors.
“ACell Inc. was able to create a product
based on this virtual information highway
that can be used for tissue healing anywhere
in the body,” said Williams. “Their product is
derived from pig urinary bladder matrix.
They remove all the cellular material and are
left with the extra-cellular matrix. Bladder tissue was chosen because there’s a high percentage of extra-cellular matrix versus cellular material.”
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The Process
The ACell Inc. products for horses are widely available, and any veterinarian may place an
order and use it for treatment. Cooper Williams VMD of Hampstead, Md., said he’s fielded
many questions from veterinarians who want more information on how to use it.
“There are always some little nuances of the actual treatment that are helpful to know,”
said Williams, who provides a short synopsis of his standard procedure for the process.
After preliminary diagnosis, confirmed with ultrasound a week after the injury—when initial swelling has dissipated, to accurately determine exact location and severity of the injury—
the horse is sedated and the reconstituted ACell mixture is injected into the site of the injury.
“I’ve had less than 1 percent of the horses I treat in which I had to do any special restraint
to do this procedure,” he said. “If I’m doing a flexor tendon, I like to do it with the injured leg
down, bearing weight, so I can feel the tendons. For suspensory lesions, if they’re up high, I’ll
have my assistant hold the leg up in the air so we can move the tendons off to the side and
get to the suspensory.”
After a thorough surgical scrub, he preps the area well. He noted it’s essential to use the
product correctly and provide proper nursing care and rehabilitation after treatment—controlled exercise and anti-inflammatory care after the injection to minimize the amount of
swelling that may occur. “The product creates a profound response in the body to start the
healing process,” he said. “The formation of new blood vessels and capillaries [that grow into
the tissues and help it heal] bring warmth and swelling, which resolves after the tissue heals.
Use of this product probably reduces recovery time by about 30 percent, but it’s very important that the rehabilitation program and gradual return to use be carefully followed.”
The word A-cell, in Latin, means not cell.
A is the Latin root for “not” (such as in the
word asymmetrical—not symmetrical).
“By using this matrix, you’re putting
into the wound a ‘mini-ecosystem.’ You’re
not just putting in one growth factor [like
IGF], you’re putting in all the growth
factors and the inhibitors as well—the little
switches that turn things on and off,” said
Williams.
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◗ It’s Like Magic
Dr. Steve Badylak is the driving force
behind the ACell Inc. In one of his early experiments, defects of the esophagus and aorta in
a dog were replaced with sheets of ACell material. The dog was re-examined after three
months and it was found that these defects
had healed without scar tissue. The dog had
regrown a functional aorta and esophagus.
“It was difficult to tell the difference,
microscopically, between the new and the
original tissues,” said Williams.
The body’s typical Band-Aid in many situations is scar tissue, to fill a hole or bridge a
gap. “They found that by using extra-cellular
matrix products, you get healing with the tissue that was intended to be there, and in a
functional manner,” he said.
The new tissue in the experimental dog,
for instance, contained the blood vessels,
nerves, and functional muscular layers of the
esophagus in proper organized fashion.
“As part of the healing, you get abundant
vascularization—new blood vessels in the
area. That’s one of the amazing things that
occurs with this treatment. There are certain
growth factors that are involved in increasing
the circulation to an area of healing, and that’s
one of the big benefits,” Williams explained.
In addition to having all the attending
growth factors and inhibitors, another benefit
of the ACell product is its ability to attract the
body’s own stem cells to an area of healing, so
they can make the proper tissues. So you’re
getting the stem cell treatment without having to put the stem cells in.
These factors are like traffic cops that
guide everything and make sure it all goes to
the right place. They bring everything into
the wound that needs to be there for proper
healing.
The product comes in different forms.
ACell Vet Powder (UBM) can be diluted in
saline, to inject into tendon and ligament
injuries.
“This is the form I’m very familiar with
because I was involved in the research for it,”
said Williams. “They also have sheets of ACell
material that can be used in wound healing and
a variety of other tissue repairs. These are
incredible, in helping heal wounds that are very
difficult—such as open wounds, severely infected wounds and burns—without scar tissue.
“They also have a corneal disc product
you can put in the eye,” he added. “ACell products can be used anywhere in the body to aid
healing processes. And what’s fascinating
about this is that after you place this product
in the body, it’s gone within a couple of
months. It becomes incorporated into the
body—it becomes part of the new tissue that
replaces it.”
◗ Research Shows
Williams and several other veterinarians
around the country have studied tendons and
ligaments treated with the powdered A-cell
material, reconstituted in saline.
Between Williams and Mitchell, more
than 275 horses have been treated with A-cell
therapy.
“We’ve seen nothing but very positive
results,” said Williams. “This is the first really
exciting thing I’ve seen, for treating tendon
and ligament injuries.”
Williams sees mostly steeplechase and
timber horses at his practice, so he’s familiar
with the many treatments touted for ligament
and tendon injuries. And so far he’s been most
impressed with A-cell therapy. He’s had
several horses in his practice that he’s sent to
Dr. Nixon at Cornell (N.Y.) for stem cell and
growth factor treatments.
“He often did these two things in conjunction. But even in comparison with these, I personally have not seen anything as exciting as
the ACell product, because of its dramatic
healing abilities,” said Williams. “I’ve not seen
anything else speed up the healing process and
give better healing, like this product.”
Williams recalled one case he received
three weeks after the initial injury, for a sec-
(Courtesy of Cooper Williams VM D)
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The fiber patterns on a tendon before A-cell
treatment, above, and after treatment,
below, where it shows marked improvement.
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A-Cell And The Sport Horse
Rick Mitchell DVM, of Fairfield Equine Associates in Newtown, Conn., has used A-cell
therapy for injuries in sport horses for the past three years. He’s found it especially useful
for suspensory ligament and suspensory branches, superficial and deep flexor tendons,
check ligament injuries and a few other tendons such as the gastrocnemius in the hind leg
at the hock.
The ACell company approached Mitchell in the spring of 2002 and asked if he and his
practice would have a clinical application for this extra-cellular membrane, the sheeted
material.
Mitchell said that if this bio-scaffold contains all the growth factors and/or stimulatory
peptides, why not use it in some sort of granulated or powdered form that could be suspended in fluid and injected into the injured tissues?
“The company initially thought we might want to use it to repair lacerated tendons, but
I told them we don’t see enough of those to bother with it,” he said. “By contrast, the number of strained or disrupted suspensory ligaments or flexor tendons is large.”
The company had already developed and powdered the product to use as a wound
dressing, so Mitchell began mixing it initially with sodium hyaluronate because it was thick.
But later he started using plain saline because he didn’t want to complicate the effects of
the trial.
“We wanted no effects other than from the ACell product,” he said.
Young horses, up to about 24 months of age, heal better than adults, which have a limited capacity to regenerate tendon and ligament tissue.
“After that, tendons and ligaments don’t heal like they should,” said Mitchell. “So the
ACell product may provide the means by which tendons and ligaments regain some ability
to regenerate.
“Our criteria for using it has been cases with significant fiber pattern disruption, as seen
on ultrasound,” he said. “We’ve done about 175 cases, and more than 100 of these are now
more than six months out from treatment. Our overall success rate in getting [the horse]
back to original function is about 82 to 83 percent.”
Mitchell finds that the toughest tissues to heal are suspensory branches. “The most success we’ve had is with proximal suspensories and superficial flexor tendons,” he added.
“Hind leg suspensories have done fairly well, but not as well as front suspensories. Hind suspensory success rate is more like 67 to 70 percent.”
This is still a high percentage of horses that heal sound enough to go back to their athletic careers, without re-injuring the site of treatment.
“Right now I’m trying to get the company to engage in formal research on how this
works,” he said. “They need to do serial dissections of limbs, which will require some
expense and donor horses. There’s been a lot of research with this product in the dog and
rabbit, but no formal research in horses.”
Mitchell presented a paper on the treatment at the American College of Veterinary
Surgeons in October 2004 in a tendon-healing seminar, and he presented information at the
British Equine Veterinary Association last September.
ond opinion. The horse had a small wound just
above the back of the ankle, over the tendon.
The horse was lame and had a large swelling
on the tendon, all the way up to the knee.
After scanning the tendon, Williams
found the superficial flexor tendon had a dissecting septic tendonitis that went from the
ankle all the way to the knee. Even though it
was just a tiny wound, infection had spread
into the tendon.
“The tendon was four times normal size,
with an appearance similar to Swiss cheese, on
ultrasound,” he said. “Many horses with this
problem end up being euthanized because
they typically don’t heal well.”
Williams consulted with Badylak. ACell
therapy was still in the research stage, and
because this was such a challenging case,
Badylak was interested in helping. And because ACell products are antibacterial, it was
an added benefit.
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“I ended up putting a double dose of
the ACell material up and down through
the tendon because there was so much
tissue involved,” said Willliams. “I could
not believe the amount of healing that
took place within the first month. It cleared
the infection, and by the second month
you could barely tell there’d been any
tendon damage at all, let alone infection.
There was a tremendous amount of healing and it had all filled in with proper
tissue.
“The horse became sound very quickly,”
he said. “And now, he’s back to doing good
work again, without any problems.”
Williams treated a number of horses last
year that are now in their timber, steeplechase
and flat racing season, and back in competition. “Several are running again and winning
races, without their legs showing any adverse
problems at all,” he said.
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