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New Leases on Life/The promise of regenerative medicine

By

Washington, D.C.-"Regenerative medicine is going to transform health care,"

declared Haseltine in his keynote remarks at the third annual

conference of the Society of Regenerative Medicine. "The goal of

regenerative medicine is to repair and restore our bodies to normal youthful

function. Our technologies have their major, but not exclusive, application

to aging."

Haseltine knows what he is talking about. He is the CEO of Human Genome

Sciences Inc., which is at the red hot center of research and development in

regenerative medicine. Haseltine also serves as the president of the society

and editor of its journal, e-biomed.

Haseltine identified four major, overlapping disciplines as comprising

regenerative medicine. "First is the use of genes and proteins from our own

bodies to restore health," he explained. "This is the gentlest intervention

imaginable. These are not foreign substances; they are the same substances

that our bodies normally use to repair and regulate themselves." Researchers

and physicians are learning how to add or subtract amounts of proteins in

order to restore normal function to damaged or diseased tissues and organs.

Doctors in Boston and San Diego have already made progress stimulating the

growth of blood vessels in damaged hearts. Other experiments have stimulated

bone growth to treat osteoporosis and muscle growth to restore aging

physiques.

"We now have at our command every piece, the genes and proteins, that our

bodies use for growth, maintenance, and repair," said Haseltine. "I believe

that there will be no cell, no tissue, no organ in the human body that we

will not be able to affect with the judicious use of proteins and

antibodies."

The second and third disciplines identified by Haseltine involve using whole

cells, both adult cells and embryonic stem cells, as individual therapies.

For example, tissue engineering-the systematic attempt to build tissues and,

eventually, entire organs-uses adult cells taken from patients. Physicians

resort to tissue engineering when they can't stimulate a patient's body to

grow and repair on its own. The concept is to build tissues and organs from

a patient's own cells outside her body for reimplantation. Already cartilage

is being taken from patients, grown outside their bodies, and reinstalled to

repair damaged joints.

Another area that is showing results is adult stem cell research. Adult stem

cells are progenitor cells that help refresh and rebuild a variety of

related tissues. Conference participant Verfaillie of the

University of Minnesota, for example, has isolated the adult stem cells that

build all of the components of the human blood system. She reports that

adult stem cells appear to be more versatile than many skeptics believe.

Verfaillie claims she can transform these adult blood-making stem cells into

various unrelated tissues, including neurons, liver cells, and endothelial

cells. Using adult cells as therapies would avoid the controversy over the

third discipline of regenerative medicine, involving human embryonic stem

cells.

Philippe Collas, a researcher from the University of Oslo, showed how his

lab has been able to directly transform skin cells into other types of

cells, some resembling (but not identical to) T cells found in the blood. He

achieves this by dosing a skin cell with an extract taken from 200 T cells.

The factors in the T cells partially reprogram the skin cell so that it

starts to act more like a T cell. The aim of this research is to find the

factors that will allow researchers and physicians to transform any type of

cell into any other type of cell.

"Research on embryonic stem cells holds the promise of not only rebuilding

organs but rebuilding them so that they are young again," said Haseltine.

Embryonic stem cells are derived from five-day-old embryos consisting of a

few hundred cells. Bowing to pressures from right-to-life activists,

President Bush decided to allow scientists dependent on federal research

funding to use only 72 stem cell lines created before August 2001. At the

conference Reubinoff, an embryologist at Hadassah University in

Jerusalem, said those 72 embryonic stem cell lines are not suitable for

clinical use as human therapies. One problem is that they were created using

mouse feeder cells that have contaminated them.

Reubinoff described how his laboratory has been able to overcome the

contamination problem with new cell lines. Furthermore, his lab has been

able to purify differentiated cells produced by maturing stem cells. This is

a crucial step because a physician would want to repair a damaged heart by

transplanting only heart cells, not a hodgepodge of brain, skin, and heart

cells. (Besides, such melanges of cells usually become cancerous.) When will

human embryonic stem cells become useful therapies? "We are still quite far

away from this goal," said Reubinoff.

Reubinoff also reported that his lab has made dramatic progress in reducing

the number of embryos needed to produce embryonic stem cell lines. He and

his colleagues have been successful 35 percent of the time. This is

important because researchers hope that someday embryonic stem cells might

be produced by cloning, that is, installing a patient's DNA into a human egg

without a nucleus. The fewer eggs it takes to create a cloned individualized

stem cell line for each patient, the more practical such a treatment

becomes. The idea is that such cloned stem cells would be transformed into

perfectly matched transplants for individual patients, avoiding the immune

rejection problem that arises when cells and organs are transplanted from

donors.

As a proof of concept for this approach to building transplantable organs,

conference participant Lanza from Advanced Cell Technologies in

Massachusetts reported on his company's success in transplanting cloned

tissues in cows. They did not suffer any immune rejection.

Many participants, including Haseltine and Ian Wilmot, the ish

scientist who cloned Dolly the sheep, believe the first success in stem cell

therapies probably will occur in treatments for neurological disorders such

as Parkinson's disease. This is because the brain is an "immune privileged"

organ, meaning it does not reject foreign tissues and cells. "I'd be

surprised if neural treatments are as many as five years away," said Wilmot.

The fourth discipline identified by Haseltine is the development of better

prosthetic devices as substitutes for failed human organs. He predicted that

materials that can detect, transmit, and provide feedback from nerve signals

will be developed in the next five to 10 years, enabling paralyzed patients

to walk. Hundreds of thousands of Americans are already walking around with

plastic heart valves, dacron aortas, and steel hip supports. Tom

Christerson, one of the seven patients who received the AbioCor artificial

hearts, has lived more than a year since it was installed.

Conference participants see a very bright if somewhat distant future for

regenerative medicine. One dark cloud on the horizon is the fear that much

research in regenerative medicine, especially embryonic stem cell research,

may be criminalized by the U.S. Congress. Reubinoff pointed out that

therapies involving embryonic stem cells may never reach patients in the

clinics without research on new embryonic stem cell lines that is forbidden

to federal researchers. Haseltine thinks many bright young researchers are

turning away from regenerative medicine because they worry that Congress

will outlaw the research. He believes Congress' opposition will change

"after the first successful treatment of a disease like Parkinson's disease

abroad. That's what happened with in vitro fertilization. It was only

approved here after it succeeded in Britain."

In the meantime, congressional intransigence is delaying the development of

treatments that could help millions. Speaking at the conference, UCLA

bioethicist Stock noted, "It will make a difference to someone who

gets cancer in 2015 whether a cure arrives in 2010 or 2025."

, Reason's science correspondent, is the editor of Global

Warming and Other Eco Myths (Prima Publishing) and Earth Report 2000:

Revisiting the True State of the Planet(McGraw-Hill).

http://www.reason.com/rb/rb120402.shtml