Giving New Life

At the McGowan Institute for Regenerative Medicine, some of the world’s best researchers are developing technologies to rebuild our nation’s wounded warriors and are healing incurable ailments. Discoveries made here will soon help benefit the civilian population as well.

With its vaulting halls and monuments commemorating the dead heroes of two centuries of warfare, the Soldiers and Sailors’ Memorial Hall & Museum in Oakland might seem an unlikely venue for a celebration of 21st-century medicine. But the event for the McGowan Institute for Regenerative Medicine that will be held there on May 25 celebrates a remarkable achievement: Researchers at the world-renowned center are finding ways to give the most grievously wounded soldiers a new life.

The McGowan Institute, a joint effort of the University of Pittsburgh and UPMC, has built artificial lungs and hearts, isolated cellular building blocks that trigger the body’s regrowth of bone, muscle and nerves and taken the first steps to grow human organs. Translating research from the lab to the hospital, the institute targets some of the toughest problems in medicine.

Today, those problems include the cases of soldiers returning from Afghanistan and Iraq with massive traumatic injuries. As doctors work to rebuild their bodies from the inside, they are finding therapies that benefit not only soldiers but civilians, too.

Breakthroughs at McGowan have been the focus of national and international news-media acclaim, including a recent feature by Morley Safer on CBS-TV’s “60 Minutes,” but the institute’s stature at the pinnacle of sophisticated medical research eludes most Pittsburghers. Stephen Badylak, director of pre-clinical studies at the institute, is happy to change that.

“Regenerative medicine is growing body parts, basically. That’s the simple way to think about it,” he begins, relaxing in a sunny conference room in McGowan’s headquarters at the Pittsburgh Technology Center, which overlooks the Monongahela River. Badylak, who has been at McGowan since 2003 has pioneered many advances in tissue engineering and directs the institute’s pre-clinical studies, one of five areas of expertise for which the McGowan is widely recognized.

More than 240 faculty members work at McGowan to develop artificial organs and medical devices, cellular therapy, tissue engineering and biomaterials, in addition to pre-clinical work. The center’s industry-relations arm pulls in companies that can fund and commercialize research results. In 2009, the center’s expenditures totaled $80 million.

“If you are going to regrow body parts, logically, what would you start with? The cell,” says Badylak. “Cell-based therapy makes [stem cells] turn into what you want them to turn into.”  The ability of embryonic stem cells to become any type of cell in the human body has generated public and political debate on the use of embryonic cells in research studies. 

McGowan scientists have focused on adult stem cells and proved they can be used to successfully regrow a dozen key tissue types, including bone, nerve, muscle and fat. They also have zeroed in on a natural biological substance that, when placed into patients, acts as a scaffold that stimulates surrounding cells to produce the exact type of tissue required.

That translational approach to research is a McGowan trademark.  “Our infrastructure is set up to allow clinicians to work with basic scientists, shoulder to shoulder, from the very earliest concepts to the clinical applications,” Badylak proudly says.  “We’ve got Eric Lagasse, a stem-cell guy in liver, next door to Mike Sachs, a bioengineer, next to Bill Wagner, a polymer chemist. Everybody’s working together because the problems we are working on can’t be solved by any single discipline. That keeps it fun.”

What’s fun for researchers is nothing less than miraculous for patients with damaged or diseased tissue and organs.

The McGowan Institute was founded in 2001, just three months after U.S. troops were dispatched to Afghanistan. William McGowan, the institute’s namesake, was the chairman of MCI Communications and received a heart transplant at UPMC. The convergence of the military’s needs and the center’s expertise became apparent as U.S. forces entered Iraq. On both fronts of the war in the Middle East, soldiers faced an insidious new weapon—bombs known as IEDs, or improvised explosive devices.

While better battlefield triage has limited fatalities, those that survive the blasts confront appalling losses: 50 percent of those injured have massive loss of muscle tissue. One-quarter suffer facial injuries. One in 10 is blinded or has eye injuries. And 7 percent incur traumatic brain injuries, “the equivalent of a stroke for soldiers,” says Badylak.

Compartment syndrome is a blast-related injury resulting from the compression of bodily tissue, which causes oxygen deprivation in the tissue and eventually destroys it. The McGowan’s success in tissue regeneration offered precisely what the military sought: A new way to help wounded veterans heal wounds and regain function.

In the past decade, defense-related institutions have pumped millions of dollars into research in Pittsburgh. Out of the federal funds that McGowan’s 30 core faculty members received in 2009, 65 percent came from  the U.S. Department of Defense, compared with 33 percent from the National Institutes of Health. Alan Russell, Ph.D., McGowan’s founding director, is co-director of the Armed Forces Institute for Regenerative Medicine (AFIRM), an $85 million federal project that comprises work at four medical centers nationwide.

The McGowan Institute and Wake Forest University lead a consortium seeking new treatments for wounded soldiers. The AFIRM partnership has already begun to apply McGowan therapies, including work by Badylak’s team, in the five programs of limb repair, craniofacial repair, burn repair, scarless wound healing and compartment-syndrome repair. Plans to launch new clinical studies that will extend beyond that partnership are expected to be announced soon.

Meanwhile, other promising stem cell research targets fat cells, a ubiquitous source.

“We’ve all got some,” chuckles plastic surgeon J. Peter Rubin. The director of McGowan’s Adipose Stem Cell Center, Rubin also investigates the basic biology of fat tissue, which contains 10 times the number of stem cells found in bone marrow. His work at McGowan suggests it may be a potent source to regenerate a variety of tissue types.

Rubin is the principal investigator in a National Institutes of Health study using adult fat stem cells for clinical soft-tissue reconstruction after cancer therapy. Active in McGowan’s AFIRM research, he also has launched a $1.6 million DoD research project that will bring 20 soldier volunteers with severe facial injuries to Pittsburgh.

“Fat grafting, or moving fat tissue from one part of the body to another, has been used as a cosmetic procedure for decades,” says Rubin.  “We are now applying these same techniques for reconstructive surgery to accurately restore facial form after battlefield injuries.”  The project uses specially designed devices and instruments for harvesting fat tissue and implanting it into regions of scarred tissue below the skin.

“Soft tissue is what creates the recognizable human form,” says Rubin, who combines his surgical practice with lab work at McGowan.  “This initial study uses only fat grafts, but subsequent studies that have already been designed will use stem cells.”

Rubin is also intrigued by the applications for fat stem cells in other systems.  “Instead of bone marrow, we could transplant fat cells to transform into blood cells,” he says.  “Albert Donnenberg at Pittsburgh’s Hillman Cancer Center is studying this in his leukemia research. It’s an amazing find.”

Research at the Adipose Stem Cell Center has discovered that fat stem cells show promise for treating nerve injuries as well: In lab rats, the therapy regenerated the sciatic nerve and restored hind-leg mobility.

With soldiers in the vanguard, patients stand to reap the benefits of current regenerative research. In the near future, Badylak anticipates regrowing human blood vessels, as well as more breakthroughs at McGowan on the biology of the central nervous system.

“All that we do for the military has civilian applications,” confirms Badylak.  “Look at the spin-offs of the space program—this is the same thing. If we figure out how to treat traumatic brain injury in soldiers, we’re probably a long way toward figuring out how to replace functional nervous tissue for stroke patients. There’s a lot of leveraging of this stuff. The field is advancing so incredibly fast.”

Christine H. O’Toole is a Pittsburgh writer who covered the story of Austin Ball, a pediatric heart patient, in last year’s Top Docs issue.

Think of regenerative-medicine research as a stream that touches most of the hospitals and biomedical research companies in the Pittsburgh region. The following projects are among dozens of inquiries gaining momentum.

Esophageal reconstruction: Half of patients undergoing surgery for esophageal cancer experience serious complications. In a recent breakthrough, a medical sleeve was coated with extra-cellular matrix and surgically implanted, replacing the patient’s cancerous organ. The esophagus grew a new functional lining that was cancer-free.

Pediatric mechanical heart: More than 35,000 babies are born each year in the United States with congenital heart defects. Nearly 9,000 require invasive treatment or surgery within their first year. PediaFlow, a magnetically powered device the size of a walnut, could be implanted in small children awaiting transplants.
  Pittsburgh’s Children’s Hospital has received NIH research funding for that device with partners World Heart and Launch Point Technologies; the team’s external pumping device, manufactured by Levitronix, also has received NIH grants.

Better breathing: Developed at McGowan and commercialized by Pittsburgh’s ALung, a local biotech company, the Hemolung System can replace or supplement ventilators—a major source of pneumonia infections—in hospital settings. The device is being implemented on a test basis at several hospitals in India and in Germany.

Using lymph nodes to grow new organs: With demand for organ transplants outstripping supply, Eric Lagasse, Pharm. D., Ph.D., has proposed a radical solution. The director of McGowan’s Cancer Stem Cell Center has created three-dimensional tissue models using lymph nodes to grow liver cells. His work, honored with the 2009 Director’s Transformative R01 Award from the National Institutes for Health, points the way to using the lymph system to manufacture liver cells, pancreas cells and other vital tissues.

Better bones: McGowan researchers have modified conventional bone cements into a product that can be shaped, or even injected, into defects to promote the regrowth of healthy bones. This effort, which may soon be in clinical trials, holds promise for repairing injuries to the bones of the face and head, as well as the rest of the body.

—Christine H. O’Toole

Categories: From the Magazine, Medicine and Health Features