Jewish World Review

Body fat may hold bonanza: Stem cells | (KRT) Every year, Americans have 150,000 gallons of fat liposuctioned out of their bodies, no doubt unaware that each pint could yield up to 200 million stem cells.

But the scientists behind that calculation are acutely aware. They enjoy pointing out that the most dispensable, detested human flesh turns out to be loaded with the elusive cells that are key to the dream of regenerating and repairing body parts.

That dream is fast taking shape, judging from a meeting in Pittsburgh earlier this month of IFATS, the fledgling International Fat Applied Technology Society.

It was only three years ago that a team from the University California Los Angeles and the University of Pittsburgh isolated stem cells from fat, technically called adipose tissue. Since that breakthrough, a flurry of experiments, mostly in animals, have revealed these cells to be surprisingly adaptable. Given the proper cues, the cells can act like - if not actually become - bone, cartilage, nerve, heart, or blood-vessel cells.

Already, fat stem cells are showing promise in reconnecting severed nerves, strengthening damaged hearts, healing inflamed intestinal holes, and cosmetically enhancing breasts.

This is tantalizing evidence that "adult" stem cells - the type found in specialized tissue such as fat and bone marrow - may have greater powers of transformation than scientists thought. Maybe not as wondrous as embryonic stem cells, which can generate every tissue and organ in the body. But then, sacrificing flab to create therapies is a lot less controversial than sacrificing embryos.

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"We have people volunteering to donate every day," said Kacey Marra, director of Pitt's plastic-surgery research laboratory as she clicked to a PowerPoint slide of one such donation - a yellow glob of liposuctioned blubber.

If the potential pans out, fat would be an ideal source for regenerative medicines for several reasons, researchers say.

A personal, or "autologous," fat supply could be readily obtained from the patient, even in an emergency. The resulting stem-cell therapy would be a genetic match, so it would not be rejected by the patient's body. And virtually everyone has fat to spare.

"Stem cells have been isolated from brain tissue, but how much brain would you be willing to give up?" quipped Patricia Zuk, research director of UCLA's Regenerative Bioengineering and Repair Laboratory. "No human tissue is as dispensable as adipose tissue. That alone makes it a very advantageous source."

Bone marrow - until now the most accessible source of adult stem cells for autologous use - must be withdrawn from the hip using a large needle. A cubic centimeter of bone marrow has about 500 stem cells, compared with 7,000 of the precious precursor cells in the same amount of fat, research shows. (Obese people do not have proportionately more fat stem cells, apparently because fatty-acid molecules dilute their adipose tissue.)

Scientists long suspected fat stem cells existed, but the team from UCLA and Pitt, led by Zuk, was the first to publish convincing evidence.

The work involved processing adipose tissue, which contains connective tissue, nerves, blood and collagen, as well as fat cells. Next, the stem cells were identified by distinctive cell-surface markers. Then, since true stem cells are able to reproduce indefinitely and "differentiate" into specialized cell types, the researchers used growth chemicals to prompt the fat stem cells in lab dishes to form colonies of cartilage, heart and bone cells.

Even so, Zuk was asked at the IFATS conference how she could be sure that fat stem cells were real - not just, say, bone-marrow stem cells that have strayed into fat. "We feel relatively confident that they are a stem-cell population," she said. "I think the problem is the definition of stem cells."

Some purists are not convinced that adult stem cells meet the criteria of being self-renewing and self-converting. Maybe these mature stem cells are simply merging or "fusing" with unrelated cells, thus appearing to change form and function. "Fusion," said Marra of Pitt's plastic-surgery research lab, "is a hot debate right now."

Other experts say that what matters most is that fat stem cells appear to have therapeutic powers, even if the precise nature of those powers isn't clear.

"It would be a home run if fat stem cells can make new heart cells," said John Fraser, who is researching such cardiovascular applications for MacroPore Biosurgery in San Diego. "But even if the stem cells are just stopping heart cells from dying, that's therapeutic."

In any case, fat stem-cell research - a field in which plastic surgeons are as numerous as molecular biologists - is advancing quickly.

Among the studies described at the conference:

At the University of Virginia, damaged hearts in mice showed improved pumping strength a month after being injected with human-fat stem cells; autopsies showed the stem cells had become engrafted in their hearts. In another experiment, fat stem cells injected into the stroke-damaged brains of rodents migrated to the injured area, although no reparative effect was shown.

At Tulane University, fat stem cells in a lab dish developed cardiac-cell characteristics, including rhythmic beating, after seven days of chemical treatment. Also, pigs with damaged hearts showed measurable cardiac improvement after treatment with stem cells from either fat or bone marrow, while the damaged hearts of untreated pigs in a comparison group got worse.

In Nice, France, government researchers have used fat stem cells to repair damaged skeletal muscles in mice.

At Pitt, researchers have been trying to repair severed sciatic nerves in rats. The limping rats' hind legs showed hints of improvement after human-fat stem cells, encased in a tiny biodegradable tube, were implanted at the severed spot in the nerve.

Only one tiny study, involving five Crohn's disease patients, has been completed so far in humans, but the results were so encouraging that a new trial with 50 patients is under way, researchers at the conference said.

Damian Garcia-Olmo, a surgeon at the University of Madrid, Spain, said he had injected fat stem cells into rectal tissue to stimulate healing of surgically repaired holes in the patients' intestinal walls. These holes, called fistulas, are a recurring complication of Crohn's, an inflammatory bowel disease. Repeated surgery to close the holes can become ineffective.

In the first study, within eight weeks of stem-cell treatment, 75 percent of the fistulas had completely healed.

"We do not know whether the stem cells differentiate into connective or muscle or scar tissue, or secrete a growth factor" that repairs inflamed cells, Garcia-Olmo told the conference.

A small trial also is under way in Tokyo to see whether fat stem cells could cosmetically enhance breasts.

J. Peter Rubin, a Pitt plastic surgeon and IFATS president, hopes the treatment can be used to rebuild breasts after cancer surgery, but questions remain, including how to control shape and size.

Fat stem cells remain mostly mysterious. What pudgy spot is the best source? Do the cells deteriorate with age? Are they the cellular version of career-changers, completely switching occupations, or more like temp workers or disaster-relief helpers?

But MacroPore Biosurgery is not waiting for definitive answers. In August, the company, led by pioneers in fat stem-cell research, obtained the crucial first patent covering the technology.

If street buzz is any predictor, their prospects are supersize: The rich and the beautiful are already bringing their liposuctioned fat to the entrepreneurs for frozen storage, banking on its future therapeutic value.

"It's sort of on the QT. But we've got a lot of patients," said MacroPore president Marc Hedrick. "Some are quite famous."

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© 2004, The Philadelphia Inquirer Distributed by Knight Ridder/Tribune Information Services