Citizen Staff Writer
UA scientists coax stem cells to grow vessels, muscle
By ANNE T. DENOGEAN
Citizen Staff Writer
The heartlike machine rhythmically pumping red liquid through clear tubes on the counter looks and sounds like a device out of Frankenstein’s laboratory.
It’s not. And Professor Stuart Williams, the University of Arizona scientist operating it, is no Frankenstein, though the analogy is hard to resist.
“That’s a nice-looking heart,” remarks a passing colleague, referring to the human tissue being nurtured in the machine called a “bioreactor.”
“Thanks,” Williams responds, “we just grew it. Can you tell?”
In Mary Shelley’s 1818 novel “Frankenstein,” Victor Frankenstein creates an artificial man while exploring the secrets of human life in his laboratory. The mad scientist ended up with a monster. Williams’ goal is far more noble.
Williams and other researchers are using adult stem cells – a special type of young cell – to create new heart parts to replace or rejuvenate damaged blood vessels and tissue.
It’s an undertaking that soon could lead to the development of replacement hearts built of components made of engineered but natural tissue.
“I don’t know how many people remember Erector sets, but it basically is the biological version of the Erector set,” Williams explained. “You say, OK, you need a wall. You need a valve. You need a blood vessel. You need vessels that are growing into the tissue to provide the nutrients and take away the waste products.
“In this wall, you need a functional cell, a pacemaker cell that will cause the heart to beat at the appropriate time. The only thing we don’t have at this point is the nerve conduits, and we’re working on that.”
Unlike Frankenstein, who operated on a shoestring budget with pilfered body parts, Williams, a professor of surgery and chair of biomedical engineering, recently received a $4 million federal grant for his research.
Shared with a private California company, Advanced Tissue Sciences, the grant from the National Institutes of Standards and Technology is allowing Williams to pursue studies of tissue regeneration. Other collaborators include scientists from Duke and Columbia universities, the University of California-San Diego and a private institute in Oregon.
The foundation of the work is the emerging knowledge of stem cells, immature cells that can develop into many types of human cells from blood to bone.
Stem cells taken from embryos are the most versatile, but stem cells taken from adults also are proving to be quite plastic, and that’s what Williams is using in his studies.
In one project that has advanced to human testing in Europe, Williams and his collaborators are using stem cells taken from a patient’s fat to grow coronary arteries to use in bypass procedures.
Bypass surgery reroutes the heart’s blood supply around clogged arteries. It’s done by transplanting a vessel from the leg or the chest. But more than 10 percent of the population doesn’t have suitable vessels for transplantation. Such people are not candidates for procedures using metallic stents, Williams said.
“What we’ve got going here is an alternative to the vessels that we pull out of the leg or we pull out of the chest,” Williams said.
Scientists learned in the 1970s that plastic tubing alone to replace blood vessels won’t work because the patient’s own cells often reject it as foreign and attack it.
In this study, the patient’s stem cells are put inside a polymer tube that acts as a scaffold for the cells. That tube is placed inside the bioreactor, which behaves as a heart would, pumping through a fluid that has all the characteristics of blood. Together, the scaffolding and the liquid coax the cells into becoming heart tissue.
After six to eight weeks – although Williams hopes to reduce that time to hours before U.S. trials – the vessel is ready for implantation into the patient’s heart. The same procedure to restore circulation from the top part to the bottom part of legs has been done in patients at UA since the 1990s.
“We haven’t done it in the heart because we needed more sophisticated bioreactors. Very simply, the blood vessels needed to be better because the heart is a more critical organ,” Williams said.
In a related project, Williams’ lab is studying how to use sheets of living tissue as cardiac patches for infarcts, areas of dead and scarred tissue and poor blood vessel growth left after heart attacks. The patch theoretically could be used with the engineered vessels or by itself for patients with lesser heart damage.
In a detail that author Shelley would have loved, the patch is grown from a single cell of foreskin tissue from a circumcised baby.
The Food and Drug Administration approved the product, Dermagraft, for treatment of burns and ulcerated wounds just three weeks ago. Use of Dermagraft as cardio patches, stitched with a few sutures onto the heart, is experimental. That use is in animal studies and moving toward clinical studies in Europe, Williams said.
The material, which can be cut to whatever shape or size is needed, resembles a layer of skin. But it is three-dimensional, filled with cells that, once put onto the body, will create healthy new tissue by stimulating the growth of new blood vessels, especially, Williams hopes, the smaller branch vessels that feed the heart.
Williams already is contemplating an improved version of the patch that would be used as a structure on which to grow the patient’s own stem cells into vessels before implantation.
“So when we put it on, it already has preformed blood vessels . . . . There’s a cute little term out there, inosculation, which is simply kissing, all those vessels have to do is kiss other vessels that are on the heart, and they form brand-new conduits,” he said.
In a third study of tissue regeneration and the heart, Williams’ lab is studying how to rejuvenate heart muscle destroyed by heart attacks and disease. The treatment, now in human trials in the Netherlands, uses stems cells culled from muscle tissue.
“There are cells in the skeletal muscle, very special cells that we can trick to becoming cardiac muscle cells. We grow them up in a culture facility and inject them into the heart in the area of an infarct. They will then become muscle cells and give them back the function of the heart,” Williams said.
“It’s absolutely amazing and not predicted by any of the models . . . . We thought we’d have to put in massive numbers of cells. It turns out you just put in a few cells in a strategic area. They migrate and crawl to the appropriate spot, proliferate a little, make all their normal connections, and you get the function back.
“Every once in a while, Mother Nature throws you an easy pitch to hit, and this was one of them. You inject these cells, and they work out quite nicely,” he said.
Williams said he envisions patient visits five to 10 years from now for “heart tuneups” to treat people before they get to the point of heart failure and a need for transplants or artificial organs.
“It’s almost preventative maintenance . . . . If you’re starting to lose vasculature in one area, we’ll tune that up. If you’re starting to lose heart muscle in one area, we’ll tune that up so the heart doesn’t lose function,” he said.
The neat thing – and admittedly the most Frankensteinish – about this work is its unlimited potential. Stem cell research, according to the National Institutes of Health primer on stem cells, has applications from Parkinson’s and Alzheimer’s disease to spinal cord injury. The techniques that Williams, his partners and other researchers across the country are developing to grow heart tissue could be used to repair or grow other organs as well.
“The is almost no realm of medicine that might not be touched by this innovation,” according to the NIH.
Even adult cells prove quite malleable
The findings may ease ethical concerns about relying on fetal tissue to grow parts for treating diabetes, stroke and other ills.
By ANNE T. DENOGEAN
Citizen Staff Writer
Stem cells are immature cells with the amazing ability to become all the different types of human cells – eyes, liver, bone, nerves and so on.
This raw gem of nature has the potential to create medical miracles.
Scientists envision using the cells to develop therapies for diabetes, arthritis, stroke, burns, heart disease, spinal cord injury, Alzheimer’s disease and basically any condition resulting from destruction of tissues or disruption of cellular function.
However, not all stem cells are alike. Some can become any type of cell. Others can give rise to most but not all tissues.
Because stem cells from embryos or fetuses are most like a blank slate of the various stem cells, they have been thought to hold the greatest promise for medical advancements. But there are huge moral questions about the use of embryonic or fetal cells.
Opponents of embryonic stem cell research say it is immoral and unethical because human embryos are destroyed in the harvesting of the cells. In August, President Bush limited federal funding of embryonic stem cell research research to 60 existing stem cell lines.
At the same time, Bush said he supported increased funding for research on stem cells obtained from adults, umbilical cords, placentas and animals.
In recent years, a growing body of research has developed to suggest that adult stem cells – found in the bone marrow, muscle and even fat – are far more malleable than had been imagined. University of Arizona Professor Stuart Williams’ heart rejuvenation research uses adult stem cells.
Dr. Curt Civins, a professor of pediatric oncology and adult stem cell researcher at the Johns Hopkins University College of Medicine, said. “I used to teach the cells you got out of the bone marrow would become all your blood cells and immune cells, and probably blood vessels. And wasn’t that wonderful? (But) they certainly don’t become your eye, your heart, your kidney. That turns out to be wrong.”
Though most scientist say it doesn’t diminish the need for research using embryonic or fetal stem cells, the appeal of using adult stem cells when possible is great for many reasons.
“There’s no problem of access to tissue or ethical issues or immune response (rejection), because the patient is his own donor. It bypasses all the ethical issues of embryonic stem cells,” said Helen Blau, adult stem cell researcher and professor and chair of molecular pharmacology at Stanford University’s College of Medicine.
ILLUSTRATION: INDUCING CELLS TO GROW IN A BIOREACTOR
Infographic by RANDY HARRIS/Tucson Citizen
PHOTO CAPTIONS: GARY GAYNOR/Tucson Citizen
A patch of human cells 10 times this size was grown from a single cell in four to six weeks. Frozen for long-term storage, the defrosted live patch can be used on skin to treat many types of injuries.
ABOVE: University of Arizona Professor Stuart Williams. LEFT: Cells grow in a polymer tube immersed in a bloodlike solution.