Stem-cell Research in Cleveland

Here, the innovative and economic impact aren't controversial.

Though the cacophonous echoes of November's election are finally fading away, at least one hotly contested issue isn't going away any time soon: stem-cell research.

Cleveland, which boasts the new Center for Stem Cell and Regenerative Medicine, is now poised at the national forefront of stem-cell research — but is not at the heart of the debate.

"Cleveland is one of the few places in the country where there's active research developing therapies in non-embryonic stem cells," says Dr. Stanton Gerson, chief of the division of hematology and oncology at University Hospitals and a professor at Case Western Reserve University.

That means that scientists here are researching adult stem cells — those found naturally in everyone's body — instead of the more controversial embryonic stem cells, a mass of cells taken from an egg fertilized in a laboratory petri dish.

Stem cells are unspecified cells that have the ability to renew themselves and, theoretically, become any part of the body: blood, tissue, muscle, organ — thus the term "regenerative medicine."

It may surprise most people to learn that stem cells are being used today, and have been for years, to cure cancer and heal bone. It's believed that, in the future, they could become the key to healing heart muscle and curing neurological diseases such as multiple sclerosis and Parkinson's disease, or even severe injuries, such as paralysis. Scientists here expect such groundbreaking discoveries to eventually emerge from the newly formed Center for Stem Cell and Regenerative Medicine.

In addition to advancing science, the center is also giving a boost to the Cleveland economy. CSCRM is financed with $20 million in state grants from Gov. Bob Taft's Third Frontier initiative. That will generate jobs, not just by bringing more stem-cell scientists to the area and staffing their laboratories, but also by generating new businesses via commercialization efforts.

Just don't go looking for a new building. The word "Center" is misleading. There isn't one central location. Instead, it is a unique collaboration between major medical facilities in Cleveland that are more used to competing than cooperating: University Hospitals, The Cleveland Clinic Foundation, Case Western Reserve University, Athersys (a Cleveland biomedical company) and one researcher at Ohio State University.

"There were communities of stem-cell researchers at these different locations, and they were hungry to have an expanded community," explains Debra Grega, Ph.D., executive director of the Center for Stem Cell and Regenerative Medicine. "This has provided a wonderful forum for exchange, discussion, new ways of looking at things."

So researchers work where they always have, but freely discuss their research across institutional borders. UH and Case share stem-cell research labs in the new Wolstein Research Building. In February, The Cleveland Clinic will open a new six-story building, currently under construction on East 96th Street. Four floors will house about 40 researchers, including many newly recruited from outside the Cleveland area, according to Paul DiCorleto, Ph.D., chairman of the Clinic's Lerner Research Institute. Eventually, the building will also house the Clinic's new Institute for Genomic Medicine, where research will focus on the genetic causes of diseases.

But long before stem cells hit the news on the campaign trail, they were news in Cleveland, when research on the cells first began decades ago. Most people, after all, have heard of bone-marrow transplants.

It turns out that it's the stem cells within the bone marrow that heal the body. So, today, most people receive "stem-cell transplants" instead of bone-marrow transplants. They are the same cells, from the same bone marrow. But within the past decade, doctors have discovered ways to mobilize the cells, to get them to move out of the marrow and into the bloodstream, where they can be nabbed more easily. Then, doctors sort the good cells from the bad and put them back into the body to cure the disease.

And that brings up the first point that Cleveland scientists want to get out in the open: All stem cells are not created equal.

"If you hear the words •stem cells,' you just have to educate yourself about the complexity of those two words," Gerson says. "It's as specific as the term 'hospital.' "

"There's all kinds. They do sort of similar things, but they can be quite different," adds Grega.

Where Do Stem Cells Originate?

There are three major sources of human stem cells: adult, umbilical cord and embryonic.

Adult stem cells are found naturally in everyone's bone marrow. Recent research indicates they may even be present in the bloodstream and other tissues, as well. But there are also numerous subsets of adult stem cells, such as cells that may become heart muscle, but couldn't possibly become brain tissue, for example.

Still, adult stem cells can be hard to track down, hiding out in the midst of other cells, at a rate of just about 20 per million cells per person. To trot out a cliché, it's like searching for a needle in a haystack.

The second source is umbilical cord blood, which is rich in stem cells. The blood from the cord, which is usually discarded, is saved immediately following the birth of a baby, with no harm to the baby. This can be stored, at a cost, for a family to use in the future or can be banked for others to use — although there still needs to be a close match.

The controversial source of stem cells is called embryonic. Embryonic stem cells come from the inner part, called a blastocyte, of a three- to five-day-old cell mass-created by the fertilization of a human egg in a petri dish. The egg is fertilized through the same process used for in vitro fertilization. When the blastocyte is removed, it continues to divide, creating a stem-cell line.

It's believed that stem cells derived from blastocytes could potentially morph into any organ or tissue needed to heal the body. (As noted above, adult stem cells may already have their destiny coded for them.) Also, since embryonic stem cells continue to divide and grow in the lab, they could be more bountiful than adult stem cells.

In the past, blastocytes used in research came from frozen embryos at fertility clinics — cells that would have been thrown away if they weren't donated to science. (They have never come from aborted fetuses as has been reported in the media.)

But on Aug. 9, 2001, President George Bush announced that only existing embryonic stem-cell lines could be used for future research that is funded by the government. Harvard University and other institutions have since raised private funding for embryonic stem-cell research.

Cleveland's Stem-cell Research

That controversial federal edict didn't affect Cleveland's scientists directly. Everyone here works only with adult human stem cells. (Some researchers, however, are working with animal embryonic stem cells, for which there is no political ruling.)

Gerson, however, won't rule out that embryonic stem-cell research could be performed in Cleveland in the future, calling it "fundamentally important" science. But he admits that, at present, scientists are "absolutely clueless" as to whether or not embryonic stem cells would turn out to be any better than adult stem cells when it comes to curing diseases.

"The argument for embryonic among the more basic scientists is that they indisputably have the capability to become any cell type," the Clinic's DiCorleto explains. "Whereas, with adult stem cells, there's still some possibilities that they can become some cells, but not all cells."

In fact, researchers don't yet know the full potential of adult-derived stem cells, either, but they have been making great strides in the lab.

Most research with adult stem cells focuses on three fundamental steps: finding and isolating the cells; growing them, so there's enough to help an adult body; and then manipulating the cells to do exactly what you want them to do, such as repair a spinal-cord injury or to grow into muscle rather than bone.

Stem-cell research takes time, however, to make sure that the cells won't cause undesirable side effects in the body. Gerson estimates that each discovery takes about eight years to get from the lab into clinical human trials.

"You're dealing with cells and they're living entities, as opposed to chemical models that you can carefully define," Grega explains. "When you're talking about doing therapies with cells, it's additional layers of complexity to make sure you can control what they're going to do and when they're going to do it."

While Cleveland scientists are well on their way to finding answers, Gerson has ambitions for the project that extend beyond the laboratory. He would like to see much more funding pumped into CSCRM and, ultimately, into the Cleveland economy.

Besides the state grants, additional funding could come from research grants from the National Institutes of Health, as well as venture capital to start stem-cell-related new businesses.

"Right now, we have about $20 million in annual funding. I don't see any reason that shouldn't be $60 [million] to $80 million within five years," he says. n

Areas of Research

Scientists at Cleveland's Center for Stem Cell and Regenerative Medicine are breaking new ground using stem cells in patients, clinical trials and basic science models. Here is some of the key research going on in the city.

• Healing bone — Dr. George Muschler at The Cleveland Clinic has patented a device called Cellect™ that helps sort stem cells from bone marrow during an orthopedic operation. The stem cells then cling to a special matrix that is placed inside the body, allowing them to grow and regenerate bone in that area.

• Repairing hearts — Researchers are exploring ways to use stem cells to grow new blood vessels in the heart to replace those that are diseased. They are also exploring ways to get stem cells into the heart to strengthen weakened heart muscle.

• Curing transplants' side effects — It sounds odd that scientists would use stem cells to cure a disease caused by a stem-cell transplant, but that's exactly what they're doing with two different types of stem cells. Stem-cell transplant patients often trade one disease for another: curing their leukemia or cancer with the transplant, but getting graft-vs.-host disease instead. In that disease, the new cells see the body's other cells as foreign invaders and begin to attack, causing a battery of symptoms. Scientists are researching to see if a particular stem cell — related to cartilage, rather than blood — would cut back on graft-vs.-host disease when given either at the time of the transplant or as a treatment once the patient develops the disease.

• Is more better? — Researchers are trying to see if stem cells from two different umbilical cords could have more impact on healing a larger adult who needs a stem-cell transplant.

• Repairing neurological damage — This is the most difficult, and in many ways the most exciting, area of stem-cell research. Because of the fragility of the brain and spinal cord, scientists admit that it may be well more than a decade before anything is tried in humans. But initial studies show promise in healing multiple sclerosis lesions, as well as in rejuvenating function after a paralyzing spinal-cord injury.

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