Discovery may heal bones, tissues

City firm's research seen as way to treat diseases, injuries

`Regenerative' medicine

April 02, 1999|By Mark Guidera | Mark Guidera,SUN STAFF

A team of scientists at a small Baltimore biotechnology company has made a breakthrough in the effort to develop revolutionary new treatments to regenerate bone, cartilage, fat and other structural and connective tissues damaged by injury or disease.

The team at Osiris Therapeutics Inc. has shown for the first time that progenitor, or "master" cells, which give rise to all other cells in the body, can be prodded in the laboratory into becoming replacement bone, cartilage, fat and other cells.

Experts said the Osiris achievement means that researchers are closer to manipulating these immature stem cells for the regeneration of diseased or damaged bones and other body parts than previously thought, and that revolutionary "regenerative" therapies may be available much earlier than expected.

Analysts consider the potential market for such therapies to be vast, noting that more than 40 million Americans suffer from debilitating bone diseases.

James Burns, Osiris' chief executive, estimated that the regeneration market could evolve into a $15 billion industry annually. Each disease or injury indication for which a stem cell product is approved for marketing has the potential to generate $1 billion in sales in the United States alone, he said.

The Osiris breakthrough is the latest in a new field of research that includes attempts to clone cells harvested from human embryos to grow human organ tissues.

"These findings are exciting and terrific," said Dr. John Gearhart, a Johns Hopkins University School of Medicine professor of obstetrics and gynecology who is considered a leading authority on progenitor cells. He headed the Hopkins team that last year stunned the scientific world when it announced that it had used fetal tissue to grow colonies of embryonic stem cells in the lab, a first step toward growing human tissues outside the body.

`Nailed this from every angle'

Daniel R. Marshak, chief scientific officer at Osiris and co-author of the article describing the work appearing today in Science magazine, said that researchers were able to control or "direct" more than 95 percent of the progenitor cells used in the experiments to develop into bone, cartilage or fat cells, depending on what researchers wanted.

"We got essentially complete and uniform cell development under tightly controlled conditions that reflect the same conditions in the body," he said. "We feel like we nailed this from every angle possible."

Experts said the most striking element of the breakthrough is that the Fells Point company has been able to re-create in the laboratory specific types of "micro-environments" found in the body. Researchers believe these environments play a key role in determining what type of cells the stem cells become.

"What is impressive is that they have come up with the right conditions which appear to recapitulate what happens in an embryo in a dish," said Gearhart. "This is one of the most important keys to success if we are ever going to be able to come up with meaningful medical therapies" from stem cells.

For example, said Marshak, Osiris researchers determined that stem cells exposed to a nutrient mix that included lots of oxygen, Vitamin C, and a specific protein, or growth factor, and a ceramic matrix structure to grow on trigger stem cells to evolve into bone cells. Meanwhile, he said, low-oxygen "tension" and a different recipe of proteins trigger stem cells to grow or "differentiate" into cartilage.

"These micro-environments have a lot to do with whether a stem cell becomes a bone cell or a fat cell or some other cell," said Mark F. Pittenger, associate director of muscle research and cell biology at Osiris and the lead author of the Science magazine article.

The team was able to grow bone, cartilage and fat cells, but its members believe they can extend their work to muscle, tendon and other connective tissues.

`Off-the-shelf' uses

Marshak said the company, which moved to Baltimore from Cleveland in 1995, is working to develop formulations which one day might allow stem cells to be "used right off the shelf" by surgeons and physicians.

The company first hopes to develop several medical therapies from its latest findings, specifically for osteoporosis and severe orthopedic injuries. It already has an experimental stem cell therapy in early human clinical trials for helping bone marrow regenerate after chemotherapy for breast cancer.

Novartis AG, the world's largest drug company, is collaborating with privately held Osiris to develop new therapies for treating bone diseases and injuries, and holds the rights to market any treatments that have commercial potential.

Said Marshak, "I personally think what we've done advances the potential for commercial applications for regenerative medicine based on stem cells by maybe seven years."

"The potential medical benefits downstream, I think, should be really significant," said Gearhart of stem cell research.

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