‘I think within ten years that we will have strategies that re-grow the bones, and promote the growth of functional tissue around those bones’ – Dr Stephen Badylak, Univ. of Pittsburgh
PIG’S BLADDER POWDER REGENERATES HUMAN TISSUE
The man who grew a finger
BY Matthew Price / 30 April 2008
In every town in every part of this sprawling country you can find a
faceless sprawling strip mall in which to do the shopping. Rarely
though would you expect to find a medical miracle working behind the
counter of the mall’s hobby shop. That however is what Lee Spievak
considers himself to be. “I put my finger in,” Mr Spievak says,
pointing towards the propeller of a model airplane, “and that’s when I
sliced my finger off.”
It took the end right off, down to the bone, about half an inch. “We
don’t know where the piece went.” The photos of his severed finger tip
are pretty graphic. You can understand why doctors said he’d lost it
for good. Today though, you wouldn’t know it. Mr Spievak, who is 69
years old, shows off his finger, and it’s all there, tissue, nerves,
nail, skin, even his finger print.
How? Well that’s the truly remarkable part. It wasn’t a transplant. Mr
Spievak re-grew his finger tip. He used a powder – or pixie dust as he
sometimes refers to it while telling his story.
Mr Speivak’s brother Alan – who was working in the field of
regenerative medicine – sent him the powder. For ten days Mr Spievak
put a little on his finger. “The second time I put it on I already
could see growth. Each day it was up further. Finally it closed up and
was a finger. “It took about four weeks before it was sealed.” Now he
says he has “complete feeling, complete movement.” The “pixie dust”
comes from the University of Pittsburgh, though in the lab Dr Stephen
Badylak prefers to call it extra cellular matrix.
The process he has been pioneering over the last few years involves
scraping the cells from the lining of a pig’s bladder. The remaining
tissue is then placed into acid, “cleaned” of all cells, and dried
out. It can be turned into sheets, or a powder.
How it works in detail
It looks like a simple process, but of course the science is complex.
“There are all sorts of signals in the body,” explains Dr Badylak. “We
have got signals that are good for forming scar, and others that are
good for regenerating tissues. “One way to think about these matrices
is that we have taken out many of the stimuli for scar tissue
formation and left those signals that were always there anyway for
constructive remodelling.” In other words when the extra cellular
matrix is put on a wound, scientists believe it stimulates cells in
the tissue to grow rather than scar. If they can perfect the
technique, it might mean one day they could repair not just a severed
finger, but severely burnt skin, or even damaged organs.
They hope soon to start a clinical trial in Buenos Aires on a woman
who has cancer of the oesophagus. The normal procedure in such cases
is often deadly. Doctors remove the cancerous portion and try to
stretch the stomach lining up to meet the shortened oesophagus. In the
trial they will place the extra cellular matrix inside the body from
where the portion of oesophagus has been removed, and hope to
stimulate the cells around it to re-grow the missing portion.
So could limbs be re-grown? Dr Badylak is cautious, but believes the
technology is potentially revolutionary. “I think that within ten
years that we will have strategies that will re-grow the bones, and
promote the growth of functional tissue around those bones. And that
is a major step towards eventually doing the entire limb.” That kind
of talk has got the US military interested. They are just about to
start trials to re-grow parts of the fingers of injured soldiers.
They also hope the matrix might help veterans like Robert Henline re-
grow burnt skin. He was almost killed in an explosion while serving in
Iraq. His four colleagues travelling with him in the army Humvee were
all killed. He suffered 35% burns to his head and upper body. His ears
are almost totally gone, the skin on his head has been burnt to the
bone, his face is a swollen raw mess. So far he has undergone surgery
25 times. He reckons he has got another 30 to go. Anything that could
be done in terms of regeneration would be great he says. “Life
changing! I think I’m more scared of hospitals than I am of going back
to Iraq again.” Like any developing technology there are many
unknowns. There are worries about encouraging cancerous growths by
using the matrix. Doctors though believe that within the so called
pixie dust lies an amazing medical discovery.
Stephen F. Badylak, DVM, MD, PhD
email : badylaks [at] upmc [dot] edu
Humans can regrow fingers? / BY Julia Layton
When a hobby-store owner in Cincinnati sliced off his fingertip in
2005 while showing a customer why the motor on his model plane was
dangerous, he went to the emergency room without the missing tip. He
couldn’t find it anywhere. The doctor bandaged the wound and
recommended a skin graft to cover the top of his right-middle stub for
cosmetic purposes, since nothing could be done to rebuild the finger.
Months later, he had regrown it, tissue, nerves, skin, fingernail and
This particular hobbyist happened to have a brother in the tissue-
regeneration business, who told him to forego the skin graft and
instead apply a powdered extract taken from pig’s bladder to the raw
finger tip. The extract, called extracellular matrix, lays the
framework that cells use to generate any given body part. It’s like a
cellular scaffolding, and all animals have it. It holds the signals
that direct cells to divide, differentiate and build themselves into a
Extracellular matrix is a component of body tissue that functions
outside of the body’s cells (thus the “extracellular” designation).
It’s made up mostly of collagen, a type of protein. So extracellular
matrix extracted from the bladder of a pig does not actually have any
of the pig’s cells in it. In human fetuses, the substance works in
concert with stem cells to grow and regrow everything from heart
aortas to toes. Fetuses can regrow almost anything that gets damaged
while in the womb. Scientists have long believed that when a fetus
reaches full development, this extracellular matrix stops functioning.
But with evidence that applying extracellular matrix from a pig can
initiate certain types of regeneration in humans, they’re wondering if
they can trigger human extracellular matrix to start working again.
After all, according to regeneration researcher Dr. Stephen Badylak of
the University of Pittsburgh, children up to the age of two have been
known to regrow fingertips with no outside help.
Pig-extracted extracellular matrix is already used by veterinarians to
help horses repair torn ligaments. In people, it’s used to treat
ulcers, closing a hole in the tissue that lines the stomach. It
employs an entirely different process than the typical mammalian
healing mechanism. Let’s take the case of a person who loses the tip
of a finger. When the finger is severed, the cells die, and their
contents seep into the surrounding tissue. This alerts the immune
system to a problem. The immune system’s response to cell death is
inflammation and scar tissue. The formation of scar tissue prevents
any future cellular development in the area. That’s why scars last —
cells are prevented from doing a repair job on that skin.
But when extracellular matrix is applied to a wound, it doesn’t
trigger an immune response. Instead, when it begins to break down into
surrounding tissue, it causes the cells in that tissue to start
repairing the damage the way they would in a developing fetus (or a
salamander that loses a limb) — they divide and rebuild, creating
new, normal tissue, not scar tissue.
Combined with developments in stem-cell research, this extracellular
matrix may work miracles in the area of regeneration science. As of
early 2007, testing of the effects of extracellular matrix is being
carried out on a military base in Texas. Scientists are using the
powdered pig extract on Iraq War veterans whose hands were damaged in
the war. They’re opening the wounds and applying the component to
finger stubs in an attempt to regrow them. The researchers conducting
the study say they don’t expect to regrow the entire finger, but are
hoping to regrow enough of a finger to allow for some utility. They
don’t believe it will regenerate bone, but nothing is for sure right
now. That man in Cincinnati had only lost his finger tip, at the lower
part of the nail; he hadn’t lost the entire finger.
Help from pigs aside, many wonder if the extracellular matrix in
humans is unable to function or is simply in a latent state, awaiting
some sort of trigger. Do humans in fact have the same regenerative
capacity as salamanders, which can regrow an entire limb, and
researchers just haven’t found a way to activate the mechanism? It’s
not just amphibians that can regrow body parts: Deer regularly regrow
lost antlers, composed of bone, tissue, cartilage and skin — the same
things that make up human limbs. Could there possibly be an internal
switch that would reactivate the regeneration capacity that humans
possess in the womb? Regenerative medicine is actively pursuing
answers to these questions. And in the meantime, if applying powdered
pig extract to a snipped finger can in fact facilitate regrowth, the
possibilities for medicine are startling. Spinal injuries, amputated
limbs and damaged organs could all be coaxed back into a complete,
healthy state if science finds the right combination of treatments.
Science Finds New Ways to Regrow Fingers
BY Malcom Ritter / February 19, 2007
NEW YORK (AP) — Researchers are trying to find ways to regrow
fingers, and someday, even limbs with tricks that sound like magic
spells from a Harry Potter novel. There’s the guy who sliced off a
fingertip but grew it back, after he treated the wound with an extract
of pig bladder. And the scientists who grow extra arms on salamanders.
And the laboratory mice with the eerie ability to heal themselves.
Powdered Pig Extract – The Stuff of Magic?
This summer, scientists are planning to see whether the powdered pig
extract can help injured soldiers regrow parts of their fingers. And a
large federally funded project is trying to unlock the secrets of how
some animals regrow body parts so well, with hopes of applying the the
lessons to humans. The implications for regrowing fingers go beyond
the cosmetic. People who are missing all or most of their fingers, as
from an explosion or a fire, often can’t pick things up, brush their
teeth or button a button. If they could grow even a small stub, it
could make a huge difference in their lives. And the lessons learned
from studying regrowth of fingers and limbs could aid the larger field
of regenerative medicine, perhaps someday helping people replace
damaged parts of their hearts and spinal cords, and heal wounds and
burns with new skin instead of scar.
A Story of Regeneration
But that’s in the future. For now, consider the situation of Lee
Spievack, a hobby-store salesman in Cincinnati, as he regarded his
severed right middle finger one evening in August 2005. He had been
helping a customer with an engine on a model airplane behind the shop.
He knew the motor was risky because it required somebody to turn the
prop backwards to make it run the right way. “I pointed to it,”
Spievack recalled the other day, “and said, ‘You need to get rid of
this engine, it’s too dangerous.’ And I put my finger through the
prop.” He’d misjudged the distance to the spinning plastic prop. It
sliced off his fingertip, leaving just a bit of the nail bed. The
missing piece, three-eighths of an inch long, was never found. An
emergency room doctor wrapped up the rest of his finger and sent him
to a hand surgeon, who recommended a skin graft to cover what was left
of his finger. What was gone, it appeared, was gone forever.
If Spievack, now 68, had been a toddler, things might have been
different. Up to about age 2, people can consistently regrow
fingertips, says Dr. Stephen Badylak, a regeneration expert at the
University of Pittsburgh. But that’s rare in adults, he said.
Spievack, however, did have a major advantage, a brother Alan, a
former Harvard surgeon who’d founded a company called ACell Inc., that
makes an extract of pig bladder for promoting healing and tissue
Federal Government Clears Use on People
It helps horses regrow ligaments, for example, and the federal
government has given clearance to market it for use in people. Similar
formulations have been used in many people to do things like treat
ulcers and other wounds and help make cartilage. The summer before Lee
Spievack’s accident, Dr. Alan Spievack had used it on a neighbor who’d
cut his fingertip off on a tablesaw. The man’s fingertip grew back
over four to six weeks, Alan Spievack said.
Lee Spievack took his brother’s advice to forget about a skin graft
and try the pig powder. Soon a shipment of the stuff arrived and Lee
Spievack started applying it every two days. Within four weeks his
finger had regained its original length, he says, and in four months
“it looked like my normal finger.” Spievack said it’s a little hard,
as if calloused, and there’s a slight scar on the end. The nail
continues to grow at twice the speed of his other nails. “All my
fingers in this cold weather have cracked except that one,” he said.
All in all, he said, “I’m quite impressed.”
Powder Being Used on Wounded Soldiers
None of this proves the powder was responsible. But those outcomes
have helped inspire an effort to try the powder this summer at Fort
Sam Houston in San Antonio, on soldiers who have far more disabling
finger loss because of burns. Fingers are particularly vulnerable to
burns because they are small and their skin is thin, says David Baer,
a wound specialist at the base who’s working on the federally funded
project. The five to 10 patients in the project will be chosen because
they have major losses in all their fingers and thumbs, preventing
them from performing the pinching motion they need to hold a
toothbrush, for example. The soldiers will have the end of a finger
stub re-opened surgically, with the powder applied three times a week.
Nobody is talking about regrowing an entire finger. The hope is to
grow enough of a finger, maybe even less than an inch, to do pinching.
And it is just a hope. “This is a real shot in the dark,” says
Badylak, who’s participating in the project. “There’s literally
nothing else these individuals have to try. They have nothing to
lose.” But from a scientific standpoint, he said, “this isn’t ready
for prime time.” For one thing, it’s not completely clear what
happened inside Lee Spievack’s finger.
Magic Finger Regrowth from Pig Cells?
The broad outline is pretty straightforward. The powder is mostly
collagen and a variety of substances, without any pig cells, said
Badylak, who’s a scientific adviser to ACell. It forms microscopic
scaffolding for incoming human cells to occupy, and it emits chemical
signals to encourage those cells to regenerate tissue, he said. Those
signals don’t specifically say “make a finger,” but cells pick up that
message from their surroundings, he said. “We’re not smart enough to
figure out how to regrow a finger,” Badylak said. “Maybe what we can
do is bring all the pieces of the puzzle to the right place and then
let Mother Nature take its course.” But “we are very uninformed about
how all of this works,” Badylak said. “There’s a lot more that we
don’t know than we do know.”
Some animals, of course, can regenerate tissue without help from any
powder. Badylak and other scientists are involved in a separate,
Pentagon-funded project to uncover and harness their secrets. This
work might someday lead to regenerating entire limbs.
One animal they’re studying is the salamander, a star of the
regeneration field. Chop off a salamander’s arm, and it will grow back
in a matter of weeks. Why? The short answer is that rather than making
a scar to heal quickly, as people do, the salamander forms a mound of
cells called a blastema. This is a regeneration factory: If you cut
off a salamander hand and transplant the resulting blastema to the
creature’s back, it will grow out a hand there.
David Gardiner at the University of California, Irvine, is studying
the secrets of the salamander by growing extra arms on the creatures.
That allows for more controlled conditions than amputating arms and
trying to follow what happens, he said. So how do you make a
salamander grow an extra arm? Make a shallow wound on the upper arm.
Re-route a nerve to the site so it will pump out critical chemical
signals that promote the creation of blastema cells. And insert a tiny
piece of skin from the other side of limb you just wounded, to help
provide a blueprint for what needs to be done. The recipe sounds like
“you put it in a cauldron under a full moon,” Gardiner observed.
The creatures are so lethargic it’s hard to tell if they can use their
extra arms, he noted. But the research shows that beyond establishing
a blueprint for a new arm, this mix of cells sends out a chemical
S.O.S. to attract other kinds of cells from the salamander’s body to
help construct a new appendage. Just how many chemical signals are
involved, and what they are, remain to be discovered.
Then there’s the specially bred mouse strain that befuddled Ellen
Heber-Katz a decade ago, and has since become a focus of her research.
Heber-Katz, of the Wistar Institute in Philadelphia, was using the
mouse strain known as MRL in a study of autoimmune diseases. Her team
punched tiny holes in the animals’ ears as markers. About three weeks
later, Heber-Katz noticed a troubling thing. “There were no ear
holes,” she recalled the other day. “We ear-punched again, and they
closed up and disappeared…. We were just so shocked.”
Like salamanders, the mice were growing blastemas instead of scars.
They also heal damage to their hearts. But for regrowing digits, even
this mouse falls short. If a toe is cut off at some point other than
the tip, the remnant produces a cell mass that looks like a small
blastema, but it doesn’t grow the missing part back. (An ordinary
mouse just develops a scar.) At least, the MRL mouse “looks like it’s
trying,” Heber-Katz said.
In studying the mice and salamanders, scientists will pursue several
questions. What genes rev up to produce regrowth? What biochemical
signals are involved? What is the role of specific cells? Can this
knowledge be used to regrow a digit on a mouse? Scientists say it’s
not clear when this research might help people. As for Spievack, the
model-airplane enthusiast, he’s had enough personal experience in this
area. “I don’t plan on cutting anything more off to find out if I can
grow that back,” he said.
email : heberkatz [at] wistar [dot] org
VIAGRA SAVING TIGERS?
Tiger Penis Soup
“This recipe was graciously given by “Miss Casey”, the head waitress
at the Pu Chung Pao resturant in Taizhong, Taiwan. If you prefer, you
can buy a bowl of this tasty?? soup for a mere 400 dollars. This
recipe makes 8 bowls of Tiger Penis Soup.
* 1 tiger penis, dried
* 24 other spices and medicines, including rhino horn, bear gall
bladder, tiger bone, and ginseng
Soak the tiger penis in water for one week. Simmer with the 24 spices
and medicines for 24-26 hours. Serves 8
Tiger Penis has long been valued by practicioners of eastern medicine
as an aphrodesiac. The penis can be taken in soup, ground in wine, or
soaked in rice alcohol for 6 months. Results vary, and recent
interviews indicate that the recent influx of Viagra into the
traditional markets of China, South Korea, and Taiwan has caused the
demand for tiger penis to drop. Apparently Viagra has more reliable
results than penis of tiger. That could also be due in part to the
common substitution of ox or deer tendons for real tiger penis by some
unscrupulous shop owners.
Medicinal uses of tiger parts has contributed greatly to the
extinction of some species of tigers, and the near-extinction of
others. Worldwide tiger populations, over 100,000 at the turn of the
century are now estimated to be around 9,000. Despite the outlawing of
killing tigers for body parts in virtually all the places where they
are found, a brisk trade still exists in tiger medicine. In April,
1999 and survey was taken of Chinese markets in New York’s Chinatown
by the Environmental Investigation Agency, an international non-profit
organization. Sixty three percent of the markets surveyed either sold
or claimed to sell goods containing tiger parts.
Traditional Chinese medicine gives body parts of certain animals the
ability to transfer the power of that animal to a human consuming or
wearing that body part. The tiger is able to mate vigorously and
repetitivly over several days. The average length of these mating is
only 15 seconds, however. hmmmmmmm.”
Other traditional uses for tiger body parts are:
whiskers – give protection from bullets, give user courage, and
eyeballs – rolled into pills, prevent and treat epilepsy and
brains – mixed with oil and rubbed over body – cures laziness and acne
bones – mixed into wine, cures rheumatism
tail – rubbed on body, said to cure skin problems
heart – cooked and eaten, imparts strength, courage, and cunning
Viagra may be saving endangered species after all / 07 October 2005
Chinese men are selectively switching from traditional Chinese
medicine (TCM) to Viagra to treat erectile dysfunction, but sticking
with tradition for ailments such as arthritis, indigestion and gout,
according to new research published in Environmental Conservation. The
finding supports a prediction made by Australian and Alaskan
researchers at the advent of Viagra’s commercial release in 1998 that
the new impotence drug might reduce demand for several species that
are over-harvested to treat impotence with TCMs. Animals such as
seals, sea horses and tigers have long been hunted because
practitioners of TCM use their body parts for their presumed healing
and virility qualities.
The researchers surveyed 256 Chinese men, aged 50 to 76, who sought
treatment at a large TCM clinic in Hong Kong. The men were questioned
about their previous and current use of TCM and Western treatments for
arthritis, indigestion, gout and impotence. The study’s lead authors
are Dr Bill von Hippel, a psychologist from the University of New
South Wales (Sydney, Australia), and Dr Frank von Hippel, a biologist
from the University of Alaska, Anchorage. The von Hippel brothers cite
three key findings from the research. “First, significantly more men
had formerly used a TCM treatment for impotence than were current
users. Second, they were significantly more likely to be using a
Western treatment for impotence than a TCM treatment. Finally, among
men who formerly used either Western or TCM treatments for impotence,
they were more likely to switch from a TCM treatment to a Western drug
than vice versa. In fact, nobody had switched from a Western drug to a
TCM treatment for impotence. “This was in contrast to their behaviour
with the other three ailments – arthritis, indigestion and gout, where
the men were more likely to be current users of a TCM treatment than a
Western treatment,” says Bill von Hippel.
These findings stand in contrast to prior research suggesting a
mistrust of Western medicine in Asian markets. “When we proposed that
Viagra might make inroads into TCM treatments for impotence,
conservationists told us we were naïve and that TCM consumers were
unwilling to use a product outside their own medical tradition,” says
Bill von Hippel. “For example, there is still strong demand for tiger
bone among TCM apothecaries who use it in the treatment of pain
relief, despite the widespread availability of aspirin.”
“But the failure to achieve an erection isn’t comparable to having a
headache or the many other ailments for which consumers still prefer
TCM treatments. Furthermore, Viagra differs from many other Western
drugs, in that the effects are rapid and visible to the naked eye. The
fact is that prior to the commercial availability of Viagra in 1998,
no product in any medical tradition had been proven to be an effective
and non-intrusive treatment of erectile dysfunction. So despite their
history of using traditional medicines and their alleged suspicions of
Western medicine, the men we interviewed chose the product that works
best,” Bill von Hippel says. These findings are consistent with
previous research by the von Hippels showing evidence of a post-Viagra
decline during the 1990s in the harvesting of three species used in
TCM impotence treatments. The pair attributed some of this decline to
Viagra, despite scepticism among many academics and wildlife experts.
In 2002, the global market for TCM products and treatments was valued
at more than $20 billion, according to the Chinese firm Shenzhen
Matrix Information Consulting.
The research was assisted by research grants from Pfizer Inc.
Frank von Hippel
email : affvh [at] uaa [dot] alaska [dot] edu / frank [at] uaa [dot] alaska [dot] edu