The Body Future

Research in regenerative medicine could someday make Steve Austin seem ordinary. Read on: You might not believe your eyes (and there’s new hope for those, too).

On March 7, 1973, Americans got their first glimpse of Steve Austin, a man barely alive. But $6 million worth of cutting-edge science (and, of course, some TV special effects) helped rebuild him into the stronger, faster, better Bionic Man.

For the next half-decade, Austin’s zoom-lens left eye and bionic limbs held our attention on the TV series “The Six Million Dollar Man,” letting us imagine that a person could actually be rebuilt with engineered parts. Each week, kids across the country were glued to their television sets, watching actor Lee Majors as covert agent Austin, who could catch any villain or foil any evil plot with the help of his remarkable, re-engineered body.

In 1982, just four years after the last episode of “The Six Million Dollar Man” aired, it suddenly seemed that fantasy was becoming reality: The world watched in astonishment as an artificial heart, the Jarvik-7, was implanted into the chest of a dying man named Barney Clark.

Clark survived for 112 well-documented days. His death was mourned worldwide, but clearly science had not failed. We had entered a new era, moving toward a day when our hearts, lungs and livers could easily be replaced if trauma or disease damaged them.

At the cutting-edge McGowan Institute for Regenerative Medicine, a joint effort of the University of Pittsburgh and UPMC, that era continues to unfold. McGowan, ranked by independent evaluations, is one of the top three regenerative medicine institutes in the world.

Teams of McGowan-affiliated engineers and scientists are tackling medical challenges and designing replacement organs that sometimes seem straight out of a sci-fi novel.

In the pages that follow, you’ll learn about 10 cutting-edge projects, including progress in conquering trauma and disease in every part of the human body. And most mind-blowing of all: Researchers are getting closer to growing entire replacement organs. Even Steve Austin would be impressed.

Some of the earliest work on artificial hearts and lungs began in the ’70s and ’80s, and in 1992, the McGowan Center for Artificial Organ Development was formally established and named after the late William G. McGowan, the CEO of MCI Communications who underwent a successful heart transplant at the University of Pittsburgh Medical Center in 1987. As work on artificial-organ devices progressed in the ’90s, research into cell therapy and tissue engineering also was growing.
 

The Body Future

10 Groundbreaking Research Projects in Regenerative Medicine
 

Battling Esophageal Cancer: Research led by Stephen Badylak, M.D., Ph.D., D.V.M.; Blair Jobe, M.D. Preclinical work is progressing for patients struggling with early esophageal cancer, known as Barrett’s esophagus. Dr. Blair Jobe has developed a technique to remove the cancerous esophageal lining and replace it with a layer of extracellular matrix (ECM) developed by Dr. Stephen Badylak. The matrix encourages stem cells to move to the site, and, over time, the lining heals into healthy tissue. With conventional surgery, the cancerous part of the esophagus is removed, and the remaining esophagus is hooked back to the stomach. A patient’s esophagus will often narrow, which makes swallowing difficult and painful. This new approach involves removing the cancerous esophagegal lining and creating a new one using ECM rather than removing the entire esophagus. The next step: clinical trials.

Conquering Type 1 Diabetes: Massimo Trucco, M.D. Dr. Massimo Trucco and his team are getting close to a cure for Type 1 diabetes, also called “juvenile diabetes.” Their research includes the isolation of a super-antigen believed to trigger juvenile diabetes in children. In their research with mice, microspheres formulated of antisense oligonucleotide (short DNA sequences) were injected under the skin near the pancreas. Nucleic-acid molecules from the microspheres were able to reprogram dendritic cells (a kind of white blood cell), which turned off the immune-system attack on insulin-producing beta cells. Just weeks later, diabetic mice began producing insulin. This unique formulation, essentially functioning as an anti-diabetes vaccine, succeeded in preventing Type 1 diabetes, and it also reversed new-onset disease. Safety testing of the vaccine in humans is underway.

Pediatric Liver Cell Therapy: Ira Fox, M.D. Dr. Ira Fox is the director of the Center for Innovative Pediatric Regenerative Therapies, a joint program of the University of Pittsburgh School of Medicine’s Department of Surgery, the McGowan Institute and Children’s Hospital of Pittsburgh of UPMC. His work focuses on finding innovative treatments for diseases resulting from liver-cell dysfunction. Other research efforts include developing alternative ways to regenerate damaged liver cells and overcoming barriers to the use of liver-cell transplantation in the treatment of hepatic diseases.

Growing “Ectopic” Organs: Eric Lagasse, Pharm.D., Ph.D. This is the final frontier: Discovering methods for growing new organs within a patient’s body to replace organs that are failing. Dr. Eric Lagasse has succeeded in getting mouse lymph nodes to grow liver cells, creating “little livers” that can then be transplanted to save an animal that would otherwise die from liver failure. The technology can potentially be applied to other organs of the human body as well.

Whole Organ Engineering: Alex Soto-Gutierrez, M.D., Ph.D. In another regenerative medicine approach to generating entire replacement organs, Dr. Alejandro Soto-Gutierrez and his team use the structural connective tissue of rat livers as a scaffold for growing new liver tissue that has been regenerated from liver cells introduced through a unique reseeding process. Building on work that Dr. Soto-Gutierrez did with researchers at Harvard University and in collaboration with Dr. Badylak, he has improved a method of flushing living cells out of the liver’s extracellular matrix, leaving behind the organ’s lobular structure, blood vessel network and growth factor proteins. Novel techniques are employed to introduce replacement liver cells through the blood vascular system back into the matrix. The experimental model suggests that an alternative strategy to organ replacement could be possible; a donor liver might be repopulated with recipient liver cells and transplanted, so rejection and the powerful drugs used to combat it would no longer be a concern.
 

 

Corneal Tissue Repair and Regeneration: James Funderburgh, Ph.D. Right now, corneal scars are treated with corneal transplants. But transplanted corneas don’t always last, and the supply of available corneas is shrinking because the increasingly common LASIK corrective vision surgery makes corneas unsuitable for transplant. So Dr. James Funderburgh is using cell-based therapies to treat human corneal blindness and vision impairment caused by the scarring that occurs after infection, trauma and other eye problems. He and his team have identified stem cells in a layer of the cornea called the stroma and have proved that, even after many rounds of expansion in the lab, the cells continued to produce the biochemical components of the cornea. After treatment with these cells, mouse eyes that initially had corneal defects looked no different from mouse eyes that were never damaged. The eventual goal of this research: to create an off-the-shelf product that will take the place of corneal transplant.

Pediatric Ventricular-Assist Device (PediaFlow): Peter Wearden, M.D., Ph.D.; Harvey Borevetz, Ph.D. Nearly 1,800 babies die annually in the U.S. as a result of congenital heart defects. And each year, approximately 60 children younger than age 5 die while waiting on the heart-transplant list for an organ donor. Right now, extracorporeal membrane oxygenation (ECMO) is the only help for these children. But if ECMO is used for more than a few weeks, severe complications develop. The tiny PediaFlow device, which is about the size of an AA battery, is designed to support patients for up to six months while a donor is found. The device, developed by Dr. Peter Wearden’s team and researchers at other facilities around the country, uses mag-lev technology to pull oxygenated blood from the left ventricle through the device. The blood is then returned to the aorta and circulates in the body. In preclinical research, it is already working for as long as 70 days. Similar LVAD-type devices save the lives of adults and older children every day. Further development and testing are moving the project toward clinical trials so that PediaFlow can save the lives of babies and toddlers.  

Muscle Healing: Stephen Badylak; J. Peter Rubin, M.D. Imagine regenerating injured muscle tissue at the cellular level: That’s being pursued in a trial conducted by Dr. Stephen Badylak and Dr. J. Peter Rubin. Patients who have lost large amounts of muscle, such as some soldiers injured by IED blasts, will be given surgery to place a tailored quilt of extracellular matrix (ECM) at the site of their injury. ECM is a protein- and growth-factor-rich biological scaffold that appears to recruit stem cells and other precursors to injury sites. The expectation is that the matrix will encourage stem cells to regenerate healthy muscle tissue. It has already been successful for Cpl. Isaias Hernandez, who was treated this way in a trial under the auspices of the Brooke Army Medical Center-San Antonio, Texas. This research is changing the lives of injured soldiers returning from the battlefield.

Blood Vessel Tissue Engineering: David Vorp, PhD.; William Wagner, Ph.D. Instead of using synthetic grafts or harvesting veins from the thigh during bypass surgery, this innovative research uses experimental blood vessels made from a biodegradable polymer shaped like blood vessels that can be seeded with stem cells. Over time, this engineered polymer will become an “ordinary” artery made from the patient’s own cells. Similar work is already happening in the treatment of larger blood vessels. This research would allow smaller-diameter blood vessels to be treated the same way, including those of the lower extremities and heart. Because of the rapid nature of the fabrication, this technology could be suitable for replacement of an injured soldier’s small-diameter blood vessel using his or her own bone marrow-derived stromal cells and an off-the-shelf available scaffold.

Craniofacial Bone Tissue Engineering: Charles Sfeir, D.D.S., Ph.D.; Prashant Kumta, Ph.D.; Bernard Costello, D.M.D., M.D. Through this clinical trial, the team will use a scaffold-like bone cement they developed that serves as a carrier of cells and growth-factor proteins. The cement, built from a biocompatible material made of simple and complex sugars, is designed to facilitate new bone formation in craniofacial defects—such as instances where there is loss of bone in the face or skull due to trauma. It can easily transition from a powder form into a paste and be shaped to fill the defect. It then hardens in place, and cells populate the gaps. Eventually, this cement dissolves completely and allows new bone to be formed that looks, feels and acts like natural bone. In preclinical trials, the risk for infection was significantly reduced, and complete reconstruction was achieved.


Eventually, these three disciplines were brought together to form the modern incarnation of the McGowan Institute. This fusion of engineering and biology has been hugely beneficial, says McGowan director Alan Russell, because researchers who worked very separately in the past now actively collaborate and share inspiration.

Tissue engineering, cellular therapies, biosurgery and the creation of artificial and biohybrid organ devices are all happening within the McGowan network.

Today, there are approximately 250 faculty members and 1,000 researchers connected to McGowan. “Probably 90 percent of those are connected with the University of Pittsburgh or UPMC,” Russell says, but others are affiliated with Duquesne University, Carnegie Mellon University, Allegheny General Hospital and other organizations.

Some are tangentially connected to McGowan, while others are “very much integrated,” says Russell. “The network is a large part of how they do their work.”

A decade ago, Russell says, many researchers assumed the idea of biologically generating whole new organs “was pie in the sky.”

“In the last couple of years, we don’t think it’s pie-in-the-sky,” he says. “In fact, the next cluster of people we hire will be dedicated to whole-organ engineering.”

Russell speaks passionately about all that’s being accomplished, yet he’s clear that a future of easily replaceable organs isn’t around the corner. “Every step forward,” he says, “is usually harder than the last one you took.”

But those difficult and life-changing steps forward are happening daily in Pittsburgh. The city has been ranked by independent evaluations as one of the top three regenerative medicine institutes in the world.
 


Melissa Rayworth writes about a mix of cultural issues—from popular culture and sexual politics to home design and parenting—for a variety of national news outlets, including The Associated Press. She lives in Allison Park with her husband and two sons.
 

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