April 26, 2002

Stem cell promise, controversy outlined at pharmacology forum

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Mark Pittenger, Ph.D., described his research with human mesenchymal stem cells from bone marrow at the forum. (photo by Dana Johnson)

Stem cell promise, controversy outlined at pharmacology forum

Stem cell research—the promise and the controversy—was the focus of this year’s Joel G. Hardman Student-Invited Pharmacology Forum last Thursday. Two speakers at the afternoon symposium discussed efforts to harness the potential of adult stem cells; the third speaker delved into the ethical debate surrounding human embryonic stem cells and therapeutic cloning.

Stem cells are the basic building blocks for the body’s many different tissues, and scientists believe that in the future these cells could be used to generate replacement cells and tissues as treatments for diseases ranging from diabetes to Parkinson’s to heart disease. These “founder” cells come in multiple varieties — from adult tissues and from embryos.

Embryonic stem cells have the potential to develop into any of the body’s different cell types. Stem cells isolated from adult tissues — the best known are blood stem cells that reside in the bone marrow — are thought to have more limited potential compared to embryonic stem cells.

The forum’s first speaker, Mark Pittenger, Ph.D., senior scientist and director of Discovery Research at Osiris Therapeutics in Baltimore, described his company’s work with one type of adult stem cell—human mesenchymal stem cells from bone marrow.

Osiris scientists have demonstrated that these mesenchymal stem cells, isolated from bone marrow and expanded to large numbers in the laboratory, will specialize and become bone, cartilage, fat, and muscle.

“We envision our product as a bag of these mesenchymal stem cells, which can be infused for different applications,” Pittenger said.

One application already in phase two clinical trials is the use of these cells for bone marrow transplant support. The cells are infused along with blood stem cells to repopulate bone marrow and improve transplant outcomes.

The company is also pursuing applications for bone regeneration, joint repair, and cardiac repair.

Perry Bartlett, Ph.D., head of the Neurobiology group at the Walter and Eliza Hall Institute of Medical Research in Melbourne, Australia, discussed brain stem cells and the possibility of using these cells to repair damage and disease in the nervous system.

“We think the way to use brain stem cells is not to transplant them, but to activate the ones that are already there,” Bartlett said.

The idea of stem cells existing in the brain is only 10 to 15 years old, Bartlett said. Good evidence now exists that the adult brain produces new neurons from populations of stem cells that reside throughout the brain and spinal cord.

In the hippocampus, an area of the brain responsible for memory, new neurons are produced on a daily basis, Bartlett said. “The study of what these new neurons are doing and their relationship to memory production is a very exciting research area.”

Bartlett and colleagues were among the first to grow brain stem cells in culture, and they have recently developed methods for isolating pure populations of these cells. Using these pure cells, he said, the investigators hope to determine the potential of neural stem cells — what types of cells they can become — and to understand the key molecules and signaling pathways involved in their differentiation and self-renewal.

The symposium’s final speaker, Ronald Green, Ph.D., director of the Ethics Institute at Dartmouth College, turned the audience’s attention to the ethical debate surrounding stem cell research.

The debate applies to human embryonic stem cells, those cells derived from early embryos — which are destroyed in the process. Green discussed three ethical questions: can we ever intentionally destroy a human embryo; can we benefit from others’ destruction of embryos; can we permit the cloning of human embryos?

It is important, Green said, to understand the biological status of the embryos used to isolate embryonic stem cells. They are five to six days old, have almost no specialized cells, cannot “think” or “feel,” have not yet established individuality, and have very limited potential to develop into a human being — in natural human reproduction, between 50 percent and 80 percent of embryos at this stage will die, Green said.

In the United States federal funds can be used for embryonic stem cell research, with constraints. The embryonic stem cell lines must have been derived prior to Aug. 9, 2001 from embryos donated by in vitro fertilization patients. Private financing can support the creation of new embryonic stem cell lines, but these lines cannot be studied using federal funds.

A thornier issue, Green said, is cloning. A bill currently before the U.S. Senate would ban all human cloning in the United States, for both reproductive and therapeutic purposes. Reproductive and therapeutic cloning both rely on a technique called somatic cell nuclear transfer. But the goal of therapeutic cloning is not to create another human being; instead, it is to isolate embryonic stem cells that match an individual. The hope is that such stem cells could be transplanted without fear of immune system rejection.

“Therapeutic cloning is really a particularly powerful stem cell technology,” Green said. “The issues surrounding cloning are complex, and our legislators do not appear up to them. They must not rush into a prohibition that doesn’t reflect the widespread feelings of Americans or the research promise in this area.”

The annual student-organized pharmacology forum, now in its 11th year, honors Joel G. Hardman, Ph.D., professor of Pharmacology, Emeritus. Hardman, who attended last week’s event, was chair of the department of Pharmacology from 1975 to 1990 and served as associate vice chancellor for Health Affairs until his retirement in 1997.

The students named the forum in honor of Hardman to recognize his commitment to graduate student education, said Joey V. Barnett, Ph.D., associate professor of Pharmacology, Medicine and Microbiology & Immunology and director of Graduate Studies in Pharmacology.

“Joel encouraged students to think outside the box,” said Barnett, who was a graduate student in the department during Hardman’s tenure as chair. “He always worked hard to get the personal best out of each student.”

Prior to the symposium presentations, Dr. Alfred L. George Jr., Grant W. Liddle Professor of Medicine and associate professor of Pharmacology, received the 2002 Teaching Award in Pharmacology.

“Teaching is fun, and it’s a privilege for me, and I’m glad you like it. I’m glad I have the opportunity to teach such great students,” George said.

The student organizers of this year’s forum were Gustav Blomquist, Lee Henage, Hilary Highfield, and Lisan Parker.