A substance extracted from pigs has allowed Marine Corporal Isaias Hernandez to regain much of the muscle he lost to a mortar explosion while serving in Afghanistan.

It was only a year ago that ACell’s “miracle powder” was sprinkled on amputated fingers and shown to stimulate the regeneration of fingertips. The world was both awed and skeptical of the powder’s regenerative power, touting that it would revolutionize regenerative medicine or calling it was quack science.

A fingertip is one thing. A thigh, quite another.

After losing most of his thigh muscle in a battlefield explosion, one marine was given a second chance when another such miracle powder caused much of his thigh to grow back. It’s not only a wonderful feel-good story, but demonstrating that the same substance can grow back different tissues suggests that we may have only seen a small part of its full regenerative potential.

October 12, 2004, Afghanistan

At the time the mortar exploded, U.S. Marine Corporal Isaias Hernandez and his companion were working to repair a truck. If he hadn’t been carrying a television at that moment he, like his companion, would have been killed. The TV absorbed most of the shrapnel, but what it missed tore through Hernandez’s arms and legs. His right thigh got the worst of it: 70 percent of its muscle was sheered off and the femur was fractured. For the next four years the Corporal underwent multiple surgeries and constant physical therapy, but his leg wasn’t getting stronger. His only option was amputation, as is the fate of the vast majority of limbs with severe muscle damage.

Enter Dr. Stephen Badylak, Director of Tissue Engineering at the University of Pittsburg’s McGowan Institute for Regenerative Medicine. Dr. Badylak and colleagues offered Corporal Hernandez an alternative to amputation: regrow the muscle. The key to this seemingly miraculous procedure is a material obtained from pig bladders. As the material’s name, the extracellular matrix implies, it is the mix of chemicals that fills the space surrounding the body’s cells. It’s a complex mixture of hormones, structural proteins, and other molecules that maintain the health and function of the cells, as well as mediates cell-to-cell communication. It also guides tissue growth. Following an intense physical therapy program to strengthen the 30 percent of muscle he had left, doctors made an incision deep into Hernandez’s thigh and applied the extracellular matrix. Instead of a powder like ACell’s, Dr. Badylak’s group turned the material into a gel form. “You can’t use a powder to replace a tendon,” remarked Dr. Badylak. It went to work, spurring not only the growth of muscle tissue but tendons, as he mentioned, and the proper vasculature as well. About six weeks after the surgery the Marine began to feel his strength returning. What’s more, he saw muscle bulking up in the area that the extracellular matrix had been applied. “I used to have a hard time walking and going up and down stairs,” he told Purdue alumnus magazine in a feature story on star alum Dr. Badylak. “I can pretty much walk and do stairs fine now.”

After more than a decade since Dr. Badylak first treated a patient with the extracellular matrix material he still doesn’t quite know how it does what it does. A few things researchers do know: the extracellular matrix becomes part of the tissue it is placed into; as part of the tissue it can grow and heal; it somehow recruits the body’s own stem cells to its location; and it changes the body’s immune response from attacking to “constructive remodeling.”

The decision to use extracellular matrix from pig bladders was not a scientific one, but an economic one. Pig parts were in abundance in butcher-happy Indiana near Purdue University where Dr. Badylak first began the research.

Pig extracellular matrix does more than just regrow thigh muscle. ACell's remarkable MatriStem powder has been used to regrow fingers.

The fact that the extracellular matrix recruits the body’s own stem cells is huge because it obviates the need to introduce stem cells from an outside source. As we’ve discussed before, even genetically-identical cells derived from the patient can be problematic. Reprogramming skin cells, for instance, into heart cells requires significant molecular manipulation, and these manipulations can lead to side effects such as rejection or cancer. The fact that the extracellular matrix puts the body’s own stem cells to work is simpler and safer. It may also get Dr. Badylak’s treatment into clinics sooner. “It…simplifies treatment because it’s much easier to get FDA approval with stem cell research when you don’t have to harvest them,” he told Purdue alumnus.

As Dr. Badylak and his colleagues know, every little bit helps. Their ‘MiracleGro For Muscles’ wasn’t always seen as such. Even after years of watching the extracellular matrix successfully morph into whatever tissue it was inserted into–from nerve cells to muscle and bone–the research stubbornly refused to get funded. As Dr. Badylak told the Purdue alumnus, “Nobody thought it was worth funding because it was such a crazy idea. Why would anyone want to put pig tissue in a human?” But profit-minded entrepreneurialism saved the day from pundit-advised conservatism. Eli Lilly and Co. and DuPuy, an orthopedic company in Indiana, put real money into the idea. With the help of drug company coffers Dr. Badylak’s research took off and eventually Washington came aboard. The current study that gave Corporal Hernandez much of his thigh back is a trial in collaboration with the U.S. government. As part of a $70 million government program for regenerative medicine, it’s hoped that Hernandez’s will be the first of many such success stories.

Given that the U.S. is currently fighting two wars, the victory for regenerative medicine couldn’t have come at a better time. “I get six to eight emails a day (from potential patients),” Dr. Badylak said in December of last year, long before news of Corporal Hernandez’s regrown thigh. Let’s hope that this treatment makes it to the clinic soon, so that Dr. Badylak can answer not only their emails, but their prayers as well.

[image credits: dailymail.co.uk, Acell]
image 1: Hernandez
image 2: Acell

Can a baby unlock the gene for strength?

The first super baby was born in Germany in 2004. Though his name was never released, pictures demonstrated that his young physique contained almost twice as much muscle as other infants. Look ahead to fall 2005 in Michigan, Mr. and Mrs. Hoekstra adopt a young boy named Liam. Soon he is growing muscle at an astounding rate. Hanging on rings in an iron cross position by 5 months, pull-ups by 9 months, Liam is the second super baby. His condition, now known as myostatin-related muscle hypertrophy, makes him hungry, lean, and strong. Check out his pic after the break.

With Liam, scientists had further proof that a genetic mutation could exist that causes a human to naturally build muscle. Without even trying, Liam has little to no body fat, can lift seven pound weights arms extended (he only weighs 30 lbs himself) and has a six-pack. Now nearly four, Liam is taking gymnastic lessons, but this is more of an outlet for his energy than an explanation for his physique. No doubts, it’s the lack of myostatin that’s helping him get ripped.

The Protein to End All Proteins

Blocking myostatin has been shown to have drastic effects in animals besides humans. Myostatin tests in labs have pumped up mice to Schwarzenegger proportions.

A whippet named Wendy has a bizarre condition that has slowed her myostatin production. A strain of cattle known as Belgian Blue are predisposed to genetic conditions that lower production of the protein…and wow, you can really tell. Looking at photos of each of these animals, I’m struck by the near absurdity of their pumpitude. It’s like someone delivered free weights to the zoo.

Which isn’t to say that the applications for myostatin blocking would be absurd. Doctors, like Louis Kunkel of the Children’s hospital in Boston, have long been searching for cures for muscular dystrophy (MD). It’s the most common genetic disease and few sufferers live into adulthood. A myostatin blocker could help these children survive and perhaps even live normal lives. All it might take is relatively small changes in the level of the protein: 20-50%.

Yet, when you type ‘myostatin’ into Google you don’t get web forums dedicated to curing muscular dystrophy. Since breakthrough research in 1997 by Alexandra McPherron, Se-Jin Lee, and Ravi Kambadur proved the effects of myostatin, the discussion has focused on one topic: blocking myostatin in order to get ripped. Buff. Cut. However you grunt it, the draw to have a treatment that creates muscle – with little exercise needed – is outweighing the medical pursuits of MD cures. Now that a human gene has been linked to myostatin-blocking I can only predict that such demand will increase dramatically. Expectedly, we can already buy “myostatin-blockers” as a workout supplement. Obviously I can’t comment on the veracity of the claims made by these products, but you may want to think about them in the same vein as other…er… ‘enlargement’ offers you receive online.

Women and Super Children First

Liam’s mother has been hesitant to allow press into her young son’s life. Rightfully she fears that the coverage would turn Liam’s existence into a circus. Even further ensconced in anonymity, the German super baby isn’t giving any interviews. However well they are shrouded from the public, however, they’ve been genetically sampled and will undoubtedly continued to be so as they mature. Using this information, it isn’t a matter of if the myostatin gene could be modified in others, it’s a matter of when.

So the demand is there, and the possibility is coming. What will it mean to have an available genetic treatment which will permanently make you able to build muscle with little effort? First, I hope it means sufferers form MD, AIDS, and other debilitating diseases will find relief from muscle atrophy. Secondly, maybe not trivially, it will mean a new series of anti-doping tests at sporting competitions. But most importantly it will be a sign that humans will be on their way to modifying their bodies to fit their lives and not the other way around.

From the 1997 study on myostatin blocking in mice. The hypertrophy is clear in two subjects.

Just recently Singularity Hub has discussed growing organs, stem cell treatments, and a wide host of bionic body augmentations (even some not so bionic additions). Genetic manipulation, however, is the real holy grail of the body-crafting endeavor. Much of this pursuit has focused on understanding the purpose of each sequence of the genome. But with myostatin, some of that completeness may be deemed unnecessary. Most people won’t be interested in discovering what a million different genes do when changing just one gives them the ideal athletes body.

That’s a recipe for disaster. We hope that Liam Hoekstra has a happy healthy life. But knowing the effects of other kinds of unchecked growth can include tough health problems, we should expect a price to come with his amazing gifts (remember Andre the Giant). We do not fully know the effects of myostatin on smooth and cardiac muscle. Organ development may benefit or be stunted. As researchers are quick to point out, ligament and tendon strength do not necessarily coincide with muscle strength. Liam already has to work a little harder on getting the flexibility common to children his age.

Myostatin genes have to be understood in the larger context before they can become part of a general genetic engineering lexicon. Let’s hope the demand for work-free muscle building will be controlled enough to wait for it. Before we can build super men we’ll have to get them the old fashioned way: by letting super babies grow up on their own.

Good luck, Liam, and watch out for Lex Luthor.