Stem cells: the first wave
As embryonic cells remain mired in ethical debate, treatments using adult cells are set to go
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Stem cells: the first wave
As embryonic cells remain mired in ethical debate, treatments using adult cells are set to go
BY ROB WATERS
BLOOMBERG NEWS
January 16, 2007
Five-month-old Luis Fernando Rojo was near death in a Miami hospital, suffering with blisters and bloody diarrhea after his tiny body rejected part of a marrow transplant for a rare bone disorder.
So U.S. regulators allowed Luis' doctors to try an unapproved therapy from Baltimore-based Osiris Therapeutics Inc. The treatment, designed to react with Luis' immune system to reduce inflammation, used adult stem cells taken from living people, not cells from embryos destroyed in a harvesting process that has spurred ethical and political debate.
Now, two years later, Luis is healthy, and the therapy, in final testing, is one of about a half-dozen adult stem-cell products that could reach the market within two years. The treatments, from companies such as Osiris, Cytori Therapeutics and Aastrom Biosciences Inc., promise to do everything from rebuilding knees and breast tissue to treating rare disorders. The use of stem cells in medicine has arrived.
On the launching pad
"It isn't about to be here, it is here now," says Christopher Thomas Scott, executive director of the Program on Stem Cells in Society at Stanford University's Center for Biomedical Ethics in Palo Alto, Calif. "The companies that will emerge first in the stem-cell arena will be those using adult stem cells." Embryonic stem cells are among the first cells created after conception. Because they can turn into any other cell type, scientists hope they may one day be used to help replace damaged or missing material in the brain, heart and immune system to cure Alzheimer's, heart disease, diabetes and other diseases. Yet, scientists agree those uses remain years away.
Ethical concerns, related to the destruction of embryos, have limited research on the cells. In 2001 President George W. Bush put into place a ban on use of federal funding for studying all but a few U.S.-approved cell lines. On Thursday the Democrat-controlled House of Representatives passed a bill bolstering embryonic stem-cell research, but the 253-174 vote fell short of the two-thirds majority needed to overturn a veto by Bush. He vetoed an identical bill last year and vowed to veto this one.
While that debate rages, research on adult cells has surged, and today scientists are studying the effects of adult stem-cell products against a range of specific medical needs.
To be sure, there are limitations. Adult stem cells, hidden in tiny numbers inside developed organs, grow into specific cell types only when the body needs them to replace or help repair a body part. As a result, some stem-cell experts say the adult cells are unlikely to provide treatments for complex disorders such as Parkinson's disease and diabetes.
Additionally, adult cells are difficult to reliably extract, and they grow for only short periods compared with embryonic cells, said Jeanne Loring of the Burnham Institute in La Jolla, Calif.
"There are pitfalls everywhere you go when you look at taking these cells from individuals and trying to use them for their own treatment," says Loring, who has studied stem cells for 20 years.
Pioneers, then and now
The idea that adult stem cells could be used to replace other types of cells originated in 1961 when two Canadian scientists showed that certain cells inside bone marrow could become all three types of blood cells: red, white and platelets. Their work paved the way for broader use of bone marrow transplants for some rare diseases and spurred a new field of research into other uses.
Osiris was the first to move the field into the commercial arena, bringing to market in 2005 a stem-cell therapy that generates new bone to treat spinal defects or hard-to-heal fractures in which the bone is shattered or pieces are missing.
More commercial products are on the way from companies using a variety of strategies.
Osiris sells stem cells from donors not related to the patient, as if they were a type of drug. Aastrom, based in Ann Arbor, Mich., will offer a service that multiplies stem cells taken from a particular patient, then sends the cells back for that person's use. La Jolla-based Cytori makes a device, to be used in hospitals or clinics, that isolates stem cells from freshly drawn fat tissue.
Osiris was founded in 1992 using technology developed by Arnold Caplan, a stem-cell researcher at Case Western Reserve University in Cleveland. Caplan showed that so-called mesenchymal stem cells can become muscle, bone, tendon or other types of tissues.
The company collects bone marrow from adult donors, isolates the mesenchymal cells, then purifies and replicates them in labs. That produces trillions of theoretically identical cells that can be shipped in intravenous bags to hospitals and kept frozen until needed.
While Aastrom and Cytori take cells from a single individual and return them to the same patient, Osiris is mass-producing stem cells, a one-cell-fits-all approach.
Experiment saves a life
One reason Osiris can produce cells from unrelated people is that the mesenchymal cells it uses don't trigger an immune reaction, like an organ transplant might, says Osiris chief executive Randal Mills. That's what allowed Osiris' product, Prochymal, to save Luis Fernando Rojo's life.
He had received a bone marrow transfusion from a partially matching donor because no fully matched donor could be located. While that cured his bone disorder, it also triggered a severe bout of graft-versus-host disease, in which immune cells in transplanted tissue attack a recipient's tissues and organs.
Doctors used Prochymal, intended for use in inflammatory diseases, after the Food and Drug Administration gave emergency approval.
"Within a week, his skin had dramatically improved, and the diarrhea had stopped," says Gary Kleiner, the University of Miami pediatric immunologist who treated him. Luis had to be treated a second time after two weeks, and Kleiner says he believes the disease is under control.
"The cells saved his life," says Nelly Rojo, the child's mother.
The company announced Nov. 9 that Prochymal cured 23 of 31 patients with graft-versus-host disease in a recent trial. Final-stage testing is under way.
Repairing intestines, knees, bones
Osiris said last week it received fast-track designation from U.S. regulators on Prochymal for Crohn's disease, an intestinal inflammatory condition, and will soon begin final-stage testing. The company's biggest potential market, though, may lie in generating knee cartilage for the 800,000 Americans who tear their meniscus each year.
The meniscus functions as the knee's shock absorber. Most who tear it have the meniscus surgically removed or repaired and accept a higher risk of developing arthritis.
Osiris' new product, Chondrogen, regenerated a functional meniscus in goats 78 percent of the time and has been injected into the knees of 55 people in a study the company plans to report on next month, chief executive Mills says.
The only adult stem-cell product on the market is Osiris' Osteocel. It is made from mesenchymal stem cells that are mixed with spongy bone material obtained from human donors or cadavers. Because the cells aren't manipulated, Osteocel is seen by the FDA as a tissue transplant, not a drug. It did not have to go through the multi-year testing and approval process that will be required of the other stem-cell products being developed by Osiris, Aastrom and Cytori.
Surgeons using Osteocel receive it in a bottle and can scoop out the cells and implant them into fracture sites. Osteocel is used in about 350 surgical procedures a month.
The main limit is obtaining cells from donors and cadavers. "We have orders that are six times our ability to supply them," Mills says.
Healing oneself
Aastrom, formed in 1991, takes bone marrow collected from patients by their doctors, processes it, then mails back the stem cells to be reintroduced into the patient's body at fracture sites. The company's method was developed by researchers at the University of Michigan in Ann Arbor. Its process manipulates and expands the cells, so extensive testing will be required to obtain FDA approval.
Aastrom is also conducting trials that use stem cells in spinal fusion, jawbone reconstruction and a rare disease, osteonecrosis, which often requires repeated hip replacements.
The company plans to begin final-stage trials for osteonecrosis in the first half of this year.
"The product with the faster path to and through the FDA we will develop and commercialize," says Aastrom chief executive George Dunbar. Using a patient's own cells eliminates any risk of rejection and should expedite FDA approval, he says.
Cytori's device emerged from work by Marc Hedrick, a plastic surgeon and now the company's president. Hedrick was doing research at the University of California, Los Angeles, when he found that fat tissue is rich in stem cells.
He initially created a company called Stem Source Inc., which was acquired in 2002 by Macrospore Biosurgery Inc. Macrospore went public in 2000 and changed its name to Cytori in 2005.
Cytori's device, the Celution System, separates stem cells from fat. The company says it hopes to begin trials this year using its cells in patients recovering from heart attacks or suffering from chronic ischemia, which is impaired blood flow to the heart.
Cells processed in Cytori's device were recently used in a trial by 11 women with breast cancer who had undergone partial mastectomies in Japan. Keizo Sugimachi, a stem-cell researcher and president of Kyushu Central Hospital in Fukuoka, injected the cells into their breasts.
Less-expensive treatment
"For mastectomies, we mix the extracted stem cells with fat, to make it easier for the cells to grow to become fat in the breast," Sugimachi says. "This technology is not suitable yet for someone who lost a whole breast but is very effective for someone whose breast was removed partially." Hedrick says he expects to provide cheaper treatments than potential competitors.
"You don't have the expense of cell culture," he says. "The cells never leave the room. It's a behind-the-scenes procedure, completely automated. The only person you need there is the nurse to push the button and pull the cells out." The company hasn't yet decided whether to sell the device or charge by the treatment, and prices haven't been set.
Adult stem cell therapies
Three U.S. companies that are developing products to regenerate or repair human tissue.
Breast reconstruction using the patient's stem cells
Company: Cytori Therapeutics
Trial completed: Breast reconstruction after partial mastectomy
Benefits: About two hour outpatient procedure that uses woman's own cells, eliminating risk of rejection.
Stem cells extracted from patient's fat are later injected into breast.
Bone repair using the patient's stem cells
Company: Aastrom Biosciences
Trial under way: Nonunion fractures
Benefits: Used for hard-to-heal fractures; uses patient's own cells, eliminating risk of rejection.
Tibia fracture
Stem cells extracted from patient's bone marrow are later inserted into fracture site.
Stem cells to treat immune system reaction
Company: Osiris Therapeutics
Now on market: Osteocel, transplantable stem cell mixture for fractures
Trials under way: Graft vs. host disease, Crohn's disease
Benefits: Uses cells from unrelated donors with no rejection problems to date.
In most cases, non-donor stem cells are transfused intravenously.
SOURCES: AASTROM BIOSCIENCES; CYTORI THERAPEUTICS; OSIRIS THERAPEUTICS; DR. GARY I. KLEINER, UNIVERSITY OF MIAMI |
