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July 24, 2003

Envisioning a new type of bionic human: Regeneration is the focus at Pitt’s McGowan Institute

When the “Bionic Man” and the “Bionic Woman” were popular on TV in the 1970s, viewers were teased with the scientific possibilities of widely available artificial replacement parts for damaged human organs and limbs.

But with the burgeoning field of regenerative medicine, that vision has become passé, according to a Pitt expert.

“If you think about the future: In 50 years’ time, if someone needed a heart valve and if we haven’t figured out how to fix that heart without all these devices like a pump or pacemaker, we, as a community, would have completely failed in our opportunity to capture the power of regeneration,” said Alan Russell, director of Pitt’s McGowan Institute for Regenerative Medicine, which this month is celebrating its second anniversary.

In July 2001, the institute supplanted the former McGowan Center for Artificial Organ Development, expanding its mission to include developing therapies that re-establish tissue and organ function impaired by disease, trauma or congenital abnormalities.

About 170 scientists, engineers and clinical faculty and some 500 adjuncts, students and staff from the Pittsburgh area comprise the McGowan Institute, located at the Biotechnology Center on Technology Drive, with a laboratory building on East Carson Street, South Side. The institute serves as headquarters for faculty developing approaches to the repair or replacement of tissues and organs through the use of cells, genes or other biological building blocks, along with bioengineered materials and technologies. The institute currently attracts about $20 million in National Institutes of Health (NIH) funding. (See sidebar story.)

The U.S. Department of Defense (DOD) also is a big player in funding, Russell said, particularly for projects related to diseases caused by weapons of mass destruction.

“If you think about how biological and chemical weapons work, they work through rapid degradation of human function,” he said. “For instance with biological weapons, you can’t rely on having a vaccine all the time. It would be great if you did, but you need treatments.”

Russell said the DOD spends almost as much as the NIH does on tissue engineering. “It’s fair to say we have here a more particular interest in defense-related uses of tissue engineering in three areas: wound-healing, musculo-skeletal and cardio-thoracic, and how to use regenerative medicine to address diseases caused by WMDs.”

Russell said that medical assisting devices will continue to play a key role, perhaps for the next 20 years, in regenerative medicine. “These devices have taught us so much, and continue to save lives all the time. But the longer-term goal surely has to be to take what we’ve learned from these devices as a first step to figure out how they can work with cell therapy and tissue engineering to get to a regenerated human that looks and performs just like the regular, healthy human,” Russell said.

As an example, Russell cited the work of Robert Kormos, McGowan Institute medical director and director of UPMC’s Artificial Heart Program, and his research team. Building on his work in the development of cardio-vascular technologies using ventricular assist devices (VADs) — battery-powered pumps that support heart function for transplant candidates — Kormos discovered a half-dozen examples of patients whose hearts regenerated enough to be taken off the organ donor waiting list.

“Dr. Kormos found that the heart was regenerating itself with the help of a device,” Russell said. “It’s a great example of what we’ve learned from the devices, but also what we’ve learned from the heart itself. Unfortunately, no one understands how it happened yet, so that’s the wonderful voyage of discovery that needs to take place between now and the future.”

While unexplained, the beneficial outcome for Kormos’s patients should not be a big surprise, Russell said. Scientists have observed for some time the regenerative powers of the human body.

“What do you do when you break a leg? You functionally unload the leg: You put a cast on it, you keep your weight off it for some period of time and the bone heals and it strengthens,” Russell said.

“It’s the same for liver injury. As long as you can provide liver function, the liver will regenerate; the lungs are the same way. Those are the two large organs we know can regenerate. So this overarching principle where we say, how can we use a device to functionally unload a damaged organ while it either recovers by itself or is triggered to recover through the application of cell therapy or tissue engineering, is a very exciting principle.”

The next steps, Russell said, are to identify what it is about particular patients that make them more disposed to device-assisted regeneration and to learn to predict which patients are going to recover and which will need a transplanted organ. “Undoubtedly, the solution will be something about the nature of the disease itself, and probably, one would guess, it would be related to the patients’ behavior once they’re on the device.”

But getting definitive answers to those questions and harnessing the body’s regenerative powers are impossible without interdisciplinary research, Russell stressed, which is why the McGowan Institute was formed as an umbrella organization, with core components of medical devices and artificial organs; tissue engineering and biomaterials; cellular therapies, and clinical translation.

“If you were to ask about how to best use VADs to encourage regeneration, clearly there’s going to be a stem cell component, because it’s the only way the heart is going to recover. There has to be a device component, so you need electrical engineers, and process-control people figuring out how that pump will work. And you need cell biologists; in this case, they have to make their preparations compatible with a pump, and not just with living tissues. And you need pre-clinical and clinical protocols.”

Russell gave other examples of cutting-edge research at the McGowan Institute, including:

• The research of Stephen Badylak, director of a McGowan Institute’s new Center for Pre-Clinical Tissue Engineering and research professor in the medical school’s Department of Surgery, who came to Pitt last January as one of the institute’s outstanding recent recruits, Russell said.

“Think about what part of your body gets damaged the most,” Russell said. “It’s the stomach that gets damaged constantly, and has to renew itself all the time. What Dr. Badylak did was take the premise that de-cellularized stomach material would retain its regenerative signals no matter where it’s put. And he proved the premise, using the lining of a pig’s stomach.”

Badylak took stomach material, removed the cells, sterilized the material and demonstrated that the material induces wound healing in humans.

“There are now 160,000 human patients worldwide who have benefited from this, making it the most successful tissue engineering project in the world as measured by patient-user number,” Russell said.

• Another new McGowan recruit, professor of surgery Jörg Gerlach, is recognized for his innovative work on biohybrid liver design, Russell said. By building bioreactor systems that combine synthetic components with human cells, Gerlach created support therapies that boost a patient’s own healing process, while a defective liver rests.

Analogous to a kidney dialysis machine, the biohybrid liver gives the liver support, which facilitates natural healing.

“He and his team are now doing the same thing here with stem cell bioreactors,” Russell said, “asking the question: Can you take adult-derived stem cells and can you culturize them in this three-dimensional complex bioreactor and have them turn into whatever tissue you want by applying the lessons he learned previously in his liver studies? This is very exciting and promising research,” Russell added.

• A third 2003 McGowan Institute recruit, Bruno Péault, is internationally recognized for his stem cell research, Russell said.

A stem cell developmental biologist with a joint appointment in pediatrics and cell biology at Pitt, Péault’s research includes identification, characterization and purification of several categories of human stem cells.

His research has focused on the characterization of human hematopoietic stem cells, and he is credited with the development of new assays for human stem cells in immunodeficient mice.

Recently, this assay system has identified the first population of stem cells in the human respiratory epithelium. His model also has been modified to create the first system in which defective lymph nodes can be maintained intact and functional for extended periods of time.

“We also have many established outstanding scientists here. But we had a very good recruiting year,” said Russell, as the institute snagged five of its six targets. “Basically, I see my job as going out and bringing in people who are a lot smarter than me,” he said.

As the first institute of its kind, the McGowan already has widespread support from the scientific community, Russell said, and lay community support is growing. Despite cutting-edge science that challenges standard treatments, “pretty much everybody looks at the end result and after seeing what it is they can support this,” he said. “We haven’t experienced any negativity at all from anyone, and the reason is that we make it clear that tissue engineering is about taking a cell and doing the 20 or 30 things you need to do to that cell before you put it into a human. It’s not about where you take that cell from. Obviously, there are a few people who don’t believe in advancing medicine, but we don’t go out of our way to offend them, and they don’t seem to go out of their way to attack us,” Russell said.

“When I try to think about our challenges, they fall in four areas. The four-Fs, as I call them: faculty, facilities, funding and facilitation. Our job as an institute is not to do the job of a department; our job is to facilitate the interactions between faculty, and between faculty and outside entities like researchers.”

—Peter Hart

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