Washington, D.C.—"Regenerative medicine is going to transform health care," declared William 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 Catherine 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 Benjamin 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 Robert 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 Scottish 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 Gregory Stock noted, "It will make a difference to someone who gets cancer in 2015 whether a cure arrives in 2010 or 2025."