October 20, 2010

iPS: an ethical alternative in stem-cell research

By Julie Filby

In 1998, James A. Thomson, a University of Wisconsin researcher, launched a moral quagmire when he became the original developer of embryonic stem-cell extraction. Because this line of research used cells harvested by killing human embryos, it created “not merely a political or ideological problem, or a problem of religious dogma,” according to the U.S. Conference of Catholic Bishops, “but a deeply human problem.”

Biomedical breakthroughs continue to develop ethically acceptable alternatives.

iPS: An ethical alternative
In 2006, Dr. Shinya Yamanaka of Kyoto University pioneered a way to reprogram ordinary cells into embryonic-like stem cells, without killing an embryo.

His discovery involved mouse skin cells. The following year Yamanaka’s laboratory, as well as Thomson’s, showed the process also worked with human skin cells. Known as induced pluripotent stem cells (iPS), these cells have revolutionized the field of stem-cell biology.

“As a substitute for embryonic stem cells, they neatly sidestep ethical dilemmas that have threatened to hold back this important area of research,” said W. Malcolm Byrnes, associate professor in the department of biochemistry and molecular biology at Howard University College of Medicine in Washington, D.C.

“Because of the ethical advantages, not only scientists but also leaders of the Catholic Church have embraced the possibilities they offer.”

Priest-scientist Father Tadeusz Pacholczyk, director of education at The National Catholic Bioethics Center in Philadelphia, closely monitors developments in iPS technology.

“Science itself may have devised a clever way to heal the wound it opened back in 1998 when human embryos began to be sought out and destroyed for their stem cells,” he said. “It’s offered a unique opportunity to declare a pause, maybe even a truce, in the stem-cell wars given that the source of these cells is ethically pristine and uncomplicated.”

iPS involves transferring four genes into adult skin or blood cells, triggering them to morph into pluripotent stem cells. Pluripotency means a cell can differentiate to become any type of cell in the body, such as skin, heart, blood or muscle cells. Tissues derived are nearly identical matches to cell donors, thus avoiding rejection by the immune system.

While induced pluripotent stem cells are derived from adult cells, it is not accurate to say they are a type of adult stem cell.

“There is confusion among the public about the difference between adult stem cells and stem cells obtained from adult cells,” Byrnes said. “Induced pluripotent stem cells are in the latter category.”

The iPS application most widely discussed in mainstream and scientific media is cellular therapy or regenerative medicine. Though these applications are believed to be years away, many companies are researching stem-cell therapy to treat diseases such as Alzheimer’s, Parkinson’s disease, spinal cord injuries and diabetes.

iPSs are useful for drug discovery and development, and disease modeling. Pharmaceutical companies can use human tissue created from stem cells to help identify potentially dangerous side-effects from drugs under development before launching human trials.

The original iPS process has drawbacks because it involves inserting genes into cells using viruses, which increases the risk that cells could cause cancer or otherwise alter behavior. The process is also inefficient, with less than 1 percent of the cells being successfully reprogrammed and used.

“Even when you’ve got it (the cell) to successfully re-program, you will still have worries about tumors or possibilities of cells ‘misbehaving’ in other ways,” Father Pacholczyk said.

New iPS development
On Sept. 30, a team led by Derrick J. Rossi of the Children’s Hospital Boston announced a new way to make induced pluripotent stem cells using synthetic messenger RNA (mRNA). mRNA carries genetic instructions but does not penetrate the DNA of target cells to trigger the steps needed to make the cells pluripotent. Researchers found it up to 100 times more efficient.

“I find this development so encouraging because there’s always been a discussion that iPS cells ‘sound good’ but when you line them up against what some call the gold standard (embryonic stem cells), they have significant differences,” said Father Pacholczyk.

“There are significant differences,” he said. “But this development shows us with a little bit of creativity and elbow grease, we’re going to be able to solve the practical limitations—and have what’s probably a very viable, if not nearly perfect, alternative to embryonic stem cells.”

According to Father Pacholczyk the Church is in favor of every ethical approach to stem-cell research. In addition to iPS cells, that includes adult stems cells derived from umbilical cords, placenta and lipids; neural adult brain cells obtained from cadavers; and germ cells.

“If we acknowledge the seriousness of the moral concerns, and yet we really want to see science go forward, we need to recognize some of the alternative approaches and focus on why the new ones are better,” he said.

Currently the legality of federal funding for embryonic stem-cell research is being contested in court. A public opinion poll conducted by International Communica-tions Research last month showed that nearly half of Americans (47 percent) oppose federal funding of stem-cell research that involves destroying human embryos.

“Research by means of induced pluripotent stem-cell technology is transforming the medical and bioethical landscape,” said Byrnes. “It holds great promise.”