Breakthrough in Stem-Cell Research

PITTSBURGH — A discovery by University of Pittsburgh medical school researchers is a boon to both families and pro-family activists.

They have found morally obtainable cells that could be stand-ins for embryonic stem cells.

Many newborns develop jaundice, a condition in which the skin has a yellow tint. But extra fluids, and sometimes a few days under special lights to dissipate the bilirubin built up in their system take care of the anomaly.

Not in the case of two of Katie and Floyd Martin's four children.

They inherited Crigler-Najjar disease and are among about 200 children around the globe born with a liver that lacks the enzyme required to process bilirubin, a blood waste product. The Martins' 12-year-old daughter had a liver transplant last year, and doctors are struggling to find an effective immuno-suppressant drug so she doesn't reject the liver.

Their 15-year-old son is on the transplant list. For now, the 6-foot, 160-pound teenager relies on the lights to keep him alive and stop bilirubin from causing brain damage.

“He's very tall and strong and healthy. It's really tough,” Katie Martin said. “I dream of gene therapy or cell therapy — something that wouldn't knock him down as hard as surgery,” said Katie, a Mennonite who has written a book, God's Golden Children.

Many of those affected in the United States are Pennsylvania-area Amish or Mennonite families.

Looking for a way to treat such conditions spurred University of Pittsburgh medical school researchers to a recently announced discovery: neonatal cells in the human placenta that bear a striking resemblance to embryonic stem cells.

The discovery may have implications far beyond the researchers' own specialty of repairing livers. In its announcement, the university said that under the right laboratory conditions, “amniotic epithelial” cells could be directed to form liver, pancreas, heart and nerve cells, and thus could be used to regenerate other tissues and organs and heal nerve damage.

Stephen Strom, associate professor of pathology, is the study's senior author. His focus is cell transplant to repair and regenerate livers, a promising therapy. “The problem is the only livers we get are the livers rejected from transplant.”

Benefit of the Doubt

Aware of the moral and ethical problems in the field of embryonic stem-cell research, Strom and his colleague Toshio Miki, focused on placentas.

“We wanted to generate a lot more cells for transplant and that's what moved us into the stem-cell field,” Strom said.

The Church has been fighting embryonic stem-cell research that requires the killing of a human embryo, which science shows is a unique boy or girl from conception to eight weeks, with their own unique DNA and normal life expectancy.

Even before stem-cell research came on the scene, the Congregation for the Doctrine of the Faith, in the 1987 instruction Donum Vitae stated that the “human being is to be respected and treated as a person from the moment of conception and therefore from that same moment his rights as a person must be recognized.”

Strom, who is also a researcher at the university's McGowan Institute for Regenerative Medicine, said he avoided conducting research with embryonic stem cells, not for religious reasons but because he is not sure when life begins.

With four million live births a year, placentas are now treated as medical waste — so there is a ready supply available, the researchers noted. The study is published online in Stem Cells Express and will appear in the journal Stem Cells. The researchers began looking at the viability of the amnion, the outer membrane of the amniotic sac, as a cell source in late 2001. The following year, the university licensed the technology to a company now called Stemnion LLC. As part of the agreement, Strom and Miki will receive license proceeds, according to the University of Pittsburgh. Both have served as paid consultants and hold equity in Stemnion.

The amnion is comprised of cells that have very similar characteristics to embryonic stem cells, including the ability to express two key genes that give embryonic stem cells their unique capability for developing into any kind of specialized cell, the researchers report.

Those two genes, Oct-4 and nanog, are required for self-renewal and pluripotency — the ability to develop into any type of cell.

The amnion, derived from the embryo, forms as early as eight days after fertilization. That, Strom surmised, means it is very close to an embryonic stem cell. He calls it a “neo-natal stem cell.”

Animal testing of placental-cell transplants into livers must take place before the federal government can approve treating people, but Strom hopes to begin experimental human-cell transplants using the cells within two to five years. Recipients would still need immuno-suppression drugs but with the cells, the body's reaction will probably be much less than with an organ transplant, Strom said. The University of Pittsburgh is a pioneer in cell transplantation.

Senate to Vote

While the Pittsburgh study appears promising from a research and treatment standpoint, it is unlikely to change the tenor of the national stem cell debate — as witnessed by the response of Pennsylvania's two senators.

The Senate is poised to vote on overturning President Bush's 2001 directive that federal funding be allowed for research using lines derived from embryonic stem cells derived prior to Aug. 9 of that year. Pro-embryonic stem-cell research Sen. Arlen Specter, R-Pa., is co-sponsoring legislation to expand that funding to include “discarded” in-vitro fertilization embryos. Senator Majority Leader Bill Frist announced this summer that he supports the bill, which passed the House of Representatives 238-194. President Bush has promised to veto it.

Asked whether the Pittsburgh findings would make a difference in Specter's stand, his spokesman, Bill Reynolds, said the senator believes “all forms of research need to go forward so you can figure out the best route to take.”

On the other hand, Sen. Rick Santorum, R-Pa., called the University of Pittsburgh discovery “just more evidence that ethical and scientifically sound alternatives to embryonic stem cells exist.”

David Prentice, scientific adviser to the Family Research Council, said the study shows the potential of adult stem cells. No cures or treatments have yet been developed using embryonic stem cells, which were first cultured in 1998.

“This report is significant because they showed not only this capability but also the lack of tumor formation, unlike embryonic stem cells,” Prentice said. “This is a wonderful source of adult stem cells.”

Strom and Miki, a pathology instructor at the University of Pittsburgh School of Medicine, found that the placental cells appear to be very similar to embryonic stem cells without two of the major embryonic stem-cell drawbacks: They do not generate random tumors, called teratomas, and they do not need to be cultured on a bed of mouse feeder cells so they avoid trace contamination.

On the other hand, they do not live virtually immortally as embryonic stem cells do, although they can still double in population about 20 times over without needing another cell type as a feeder cell layer.

Others are also exploring the potential of these placental cells, Strom noted.

He hopes to apply cell transplantation to children with Crigler-Najjar disease soon. Katie Martin is right to worry, Strom said, “This is a lethal disease.”

“My son's between a rock and hard place. What's he supposed to do?” asked the Mifflinburg, Pa., mother. “He's seen what his sister's gone through, and yet he knows what happens if he waits too long. We just pray for direction, for the right thing to do.”

Valerie Schmalz is based in San Francisco, California.