Months later, he had regrown it, tissue, nerves, skin, fingernail and all.
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.
“Yes, it is,” Badylak explained. “We took this and turned it into a powdered form.” That powder is a substance made from pig bladders called extracellular matrix. It is a mix of protein and connective tissue surgeons often use to repair tendons and it holds some of the secrets behind the emerging new science of regenerative medicine.
“Somehow the matrix summons the cells and tell them what to do,” Badylak explained. “It helps instruct them in terms of where they need to go, how they need to differentiate – should I become a blood vessel, a nerve, a muscle cell or whatever.” If this helped Spievack’s finger regrow, Badylak says, at least in theory, you should be able to grow a whole limb.
Advances That Go Beyond Theory In his lab at Wake Forest University, a lab he calls a medical factory, Dr. Anthony Atala is growing body parts. Atala and his team have built, from the cell level up, 18 different types of tissue so far, including muscle tissue, whole organs and the pulsing heart valve of a sheep. “And is it growing?”Andrews asked. Absolutely,” Atala said, showing him, “All this white material is new tissue.”
“When people ask me ‘what do you do,’ we grow tissues and organs,” he said. “We are making body parts that we can implant right back into patients.”
Atala’s work with human bladder cells has pushed regenerative medicine to a transformational breakthrough.
In this clinical trial at Thomas Jefferson Hospital in Philadelphia, Dr. Patrick Shenot is performing a bladder transplant with an organ built with this patient’s own cells. In a process developed by Dr. Atala, the patient’s cells were grown in a lab, and then seeded on a biodegradable bladder-shaped scaffold. Eight weeks later, with the scaffold now infused with millions of regrown cells, it is transplanted into the patient. When the scaffold dissolves, Dr. Shenot says what’s left will be a new, functioning organ. “The cells will differentiate into the two major cells in the bladder wall, the muscle cells and the lining cells,” he explained. “It’s very much the future, but it’s today. We are doing this today.”
Repairing The Wounded
Today, one of the biggest believers in regeneration is the United States military, which is especially interested in the matrix that regrew Lee Spievack’s finger. The Army, working in conjunction with the University of Pittsburgh, is about to use that matrix on the amputated fingers of soldiers home from the war. Dr. Steven Wolf, at the Army Institute of Surgical Research, says the military has invested millions of dollars in regenerative research, hoping to re-grow limbs, lost muscle, even burned skin. “And it’s hard to ignore this guys missing half his skin, this guy’s missing his leg,” Wolf said. “You start asking the question, is there somebody out there with the technology that can do this for us?”
You mean regrow the tissue?” Andrews asked. “The answer,” Wolf said, “is maybe.” At the burn unit at the Brooke Army Medical center, the very idea of regeneration brings a glimmer of hope.
Army Staff Sgt. Robert Henline was the only survivor of an IED attack on his Humvee north of Baghdad. “It’s a great idea,” Henline said, talking withAndrews about the military’s investment into the new technology. “If they can come up with something that’s less painful and can heal it with natural growth, without all this scarring, it’s definitely something to check into.”
Corporate America, meanwhile, already believes regeneration will work. Investment capital has been pouring in to commercialize and mass produce custom-made body parts. The Tengion Company has bought the license, built the factory, and is already making those bladders developed at Wake Forest that we told you about earlier. “We’re actually building a very real business around a very real and compelling patient need,” said Dr. Steven Nichtberger, Tengion’s CEO. Tengion believes regeneration will soon revolutionize transplant medicine. Transplant patients, instead of waiting years for a donated organ, will ship cells off to a lab and wait a few weeks to have their own re-grown. “I look at the patients who are on the waitlist for transplant,” said Nichtberger. “I look at the opportunity we have to build bladders, to build vessels, to build kidneys. In regenerative medicine, I think it is similar to the semi-conductor industry of the 1980s, you don’t know where it’s going to go, but you know it’s big.”
For more on regenerative medicine and organ transplants, check out:
The McGowan Institute for Regenerative Medicine. The non-profit United Network for Organ Sharing. The non-profit Organ Procurement and Transplantation Network. The non-profit organ and tissue donation group, Gift Of Life Organ Donation. Wake Forest University. Tengion Company.
- How Cells Work
- How Stem Cells Work
- How the Immune System Works.ScienceMagazine: What Controls Organ Regeneration? – July 1, 2005
- University of Guelph: Deer antlers may teach humans how to regrow body parts – May 19, 2000
- Wired News: Science Finds New Ways to Regrow Fingers – Feb. 19, 2007
- “Deer antlers may teach humans how to regrow body parts.” University of Guelph. May 19, 2000.
- “Doctors seek to regrow parts of fingers.” NewsTrack. Feb. 14, 2007.
- Ritter, Malcolm. “Science Finds New Ways to Regrow Fingers.” Wired News. Feb. 19, 2007.
- Windslow, Ron. “Human regrowth Doctors try new techniques to restore certain body parts.” News-Sun. Feb. 19, 2007.