National Catholic Register

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New Stem-Cell Discovery May Sidestep Ethical Debate

BY EDWARD MULHOLLAND and ELIZABETH KELLEY

Register Correspondents

August 27-September 2, 2006 Issue | Posted 8/28/06 at 10:00 AM

 

LOUISVILLE, Ky. — When Joseph Grimaldi suffered a relapse of a childhood bone cancer and needed a stem-cell transplant, he stood on principle.

“I told the doctor there was no way I would be treated with embryonic cells,” the Florida teenager recounted. “My principles and my faith come before my health.”

Unfortunately, his own body didn’t produce enough adult stem cells for a successful transplant. He and his family are hoping that chemotherapy has finally knocked out all traces of his Ewing’s sarcoma.

If research with human embryonic stem-cell research finds cures, millions of Americans may face a dilemma similar to Grimaldi’s. Will patients be forced to choose between standing on principle and suffering on the one hand and undergoing treatments derived from human embryos denied a chance to develop and grow toward birth on the other?

A human embryo is a unique boy or girl from conception to eight weeks, with DNA, life-expectancy — and the right to life.

Stem cells are cells in the bone marrow that have the ability both to multiply and to differentiate into specific blood cells and other cell/tissue types. This ability allows them to replace cells that have died, and they have been used to replace defective cells and tissues.

Embryonic stem-cell research, which involves the killing of a unique human being, has proven not only destructive and costly, but has not produced a cure. Adult stem-cell research, which uses cells from adult tissues or umbilical cords, does not require the destruction of human life. It has proven successful in treating different kinds of cancers and autoimmune diseases such as multiple sclerosis.

Pope John Paul II said that all research using stem cells from human embryos is “morally unacceptable.”

In his 1995 encyclical Evangelium Vitae (The Gospel of Life), John Paul said, “This moral condemnation also regards procedures that exploit living human embryos and fetuses — sometimes ‘produced’ for this purpose by in vitro fertilization — either to be used as ‘biological material’ or as providers or organs or tissue for transplants in the treatment of certain diseases.

“The killing of innocent human creatures, even if carried out to help others, constitutes an absolutely unacceptable act.”

President Bush’s July 19 veto of federal funding for human embryonic stem-cell research laid the matter to rest — for a while. While research advocates are not resting, a new discovery promises to sidestep the ethical debate.

A team of scientists from the University of Louisville’s James Graham Brown Cancer Center stem-cell biology program, led by Dr. Mariusz Ratajczak, have isolated some tiny cells in mouse bone marrow that act indistinguishably from embryonic cells. They have successfully cultured marrow cells, once thought to be useful only for renewing blood cells, into the major tissue types, including brain, nerve, heart muscle and pancreatic cells.

The results, published in the scientific journal Leukemia in February, raised hopes that similar results can be done with human cells. Successes with human cells are now being reported.

These cells, called Very Small Embryonic Like cells or VSELs, behave exactly like embryonic cells, but, since they do not require the destruction of an embryo, their use is morally acceptable.

Ratajczak’s training as a hematologist and oncologist — studying diseases of the blood with a focus on leukemia — led him to believe that there were cells in adult human bone marrow that had not been fully characterized from the standpoint of their scientific and medical potential.

‘Newborn’ Cells

Bone marrow and umbilical cord blood are known to contain what are called hematopoietic (blood-making) stem cells. They are useful in treating blood diseases like leukemia. Nobody had ever taken a close look at the entire population of bone marrow/cord blood cells to determine exactly what the mechanism is that helps
treat these diseases; they just assumed it was a mechanism of the blood-making cells.

“In all of these deliberations concerning stem-cell plasticity, the concept that (bone marrow) may contain heterogeneous populations of stem cells was surprisingly not taken carefully enough into consideration,” Ratajczak told the Register. “We postulated that the presence of heterogeneous populations of stem cells in [bone marrow] tissue should be considered first. … This led us to the identification of very small embryonic-like stem cells in the adult bone marrow tissue.”

He is guardedly optimistic that his VSELs may be just as good as embryonic stem cells for research.

“These cells could be an alternative, but today we do not have enough data to tell which cells from ‘the biological’ point of view would perform better as a source of cells for regeneration,” he said. “What I can tell you today is this: that our preliminary data suggest that these cells will be very similar in their biological potency.”

His study garnered an Editor’s Choice award from Nature Publishing Group, which is responsible for 65 scientific journals. Since then, Ratajczak’s team has seen its own results confirmed and duplicated in five laboratories, including Mount Sinai School of Medicine in New York, and the University of Illinois, where scientists have isolated similar cells in human cord blood samples. The Illinois group presented their results at the annual meeting of the International Society of Stem Cell Researchers, which was held June 17-21 in Toronto.

“The confirmation is extremely promising,” says Dr. Gerry Sotomayor, director of the Babies for Life Foundation in Atlanta, which promotes umbilical cord blood donation for stem cell transplants. “We met with Dr. Ratajczak in March, and since then we have been sending him human cord blood samples. He has been able to isolate VSEL cells in humans, and we hope to form the major tissue types from them.”

If the results pan out, so-called adult stem cells (some have begun to call them “newborn stem cells”) may turn out to be as pluripotent (capable of producing many tissue types) as embryonic cells, which is exactly why many in the scientific community have insisted on the latter.

No Rejection

An advantage VSELs would hold over embryonic cells is that they can come from the patient, and thus avoid the danger of rejection which donated cells incur. Still, they may share the problem that embryonic cells have had until now: They are difficult to control, and can develop into a tissue type other than the one intended, causing cancerous tumors called terratomas. Though acknowledging the difficulty, Ratajczak remains hopeful and confident in his Louisville team.

“Currently, we are working on developing appropriate strategies to differentiate these cells derived from the VSELs-derived clusters into tissue-specific cells that will not grow terratomas in mice,” he said

VSEL cells may be just the kind of “embryonic-type” cells that a member of the President’s Council on Bioethics advocated in May 2005.

“I support the council’s efforts to identify means of obtaining human pluripotent stem cells for biomedical research that do not involve killing or harming human embryos and do not invite the exploitation of women to obtain ova,” Robert George of Princeton University said at the time. “If such means can be identified, research involving embryonic or embryonic-type stem cells could go forward, and be funded by the federal government, without ethical qualms and controversy.”

Sotomayor, of the Babies for Life Foundation, said that not only cord blood, but placenta and other tissues resulting from human birth are particularly rich in VSEL cells.

“We are debating about federal funds for embryonic cells that require the destruction of life, yet we throw away something morphologically and functionally identical every day,” he said.

His foundation is pushing for the “universal collection” of these tissues after every birth. “Doing it for every birth will result in a public resource of great genetic diversity,” said Sotomayor, who recently left his OB/GYN practice to fully dedicate himself to research and postnatal tissue collection.

In April, Georgia Gov. Sonny Perdue signed an executive order creating the Governor’s Commission for Newborn Umbilical Cord Blood Research and Medical Treatment. The commission will establish a network of postnatal tissue and fluid banks in partnership with universities, hospitals, nonprofit organizations and private firms in Georgia for the purpose of collecting and storing postnatal tissue and fluid. Until now, cord blood banks have been a private matter.

Stem-cell transplants from cord blood have a 50%-60% success rate. One private laboratory, however, Stemcyte in Arcadia, Calif., boasts an 85%-90% success rate. Sotomayor hypothesizes that VSEL cells may hold the key to the higher rate.

“In most laboratories, the samples are subjected to a cleansing process. Stemcyte, while treating the samples with utmost care, doesn’t put them through the wash,” he said. “The tiny VSEL cells are lost in many samples in other labs. They must aid the transplant in ways we are just beginning to understand.”

Ratajczak concurred, explaining that the VSELs are a support for the transplant’s “take” or “engraftment,” and added, “This would be in particular important for hematopoietic transplants performed with human cord blood.”

More Data Needed

Dr. Hans-Willem Snoeck of Mount Sinai School of Medicine’s Department of Gene and Cell Medicine, while admitting that Ratajczak’s discovery is interesting, added a word of caution. “The Mount Sinai lab found different cells from those found by Dr. Ratajczak, although they are also embryonic-like. It is very difficult to replicate findings exactly at the adult stem cell level.”

He also told the Register that VSELs, even when differentiated, are at this point different from embryonic cells.

“Calling them ‘functionally equivalent’ is a bit misleading. Embryonic cells can be grown virtually ad infinitum and VSELs can’t be grown at all,” he said. “These cells have been differentiated to have the markers of other tissue types, but that isn’t the same thing as forming tissue types such as pancreatic cells that will behave as such in a patient. Also, since these cells are only about .02% of bone marrow cells, their value is very limited unless we develop technology to grow them.

“Promising? Yes. Revolutionary? Not yet. Much more data is still needed.”

Edward Mulholland

and Elizabeth Kelley are

based in Cumming, Georgia.