Amniotic Stem Cells Offer Alternative to Embryonic

Stem cells from amniotic fluid may open a third avenue of research for scientists seeking to regenerate human tissue that is less controversial than embryonic cells and more versatile than adult stem cells.

The amniotic cells don't carry the same ethical and political concerns as stem cells harvested in a way that requires destruction of embryos. They also are easier to work on in the laboratory than adult stem cells, and may be able to grow into a wider variety of cells, the researchers said.

The finding may help kick-start use of amniotic cells by companies seeking to develop therapies for disease such as Parkinson's, Alzheimer's or diabetes. The amniotic cells are equally as capable as embryonic cells in forming fat, liver, nerves, blood vessels and other tissue, the researchers said.

``This is a third class of stem cell that is derived from the fetus and routinely available with amniocentesis,'' said Kenneth Chien, director of the cardiovascular disease program at the Harvard Stem Cell Institute in Boston and a Massachusetts General Hospital cardiologist. ``These cells are falling somewhere in between.''

Amniocentesis, in which a needle is used to remove fluid from the womb for testing, is routinely used during pregnancy.

Embryonic stem cells are the first cells created after conception. Because they can turn into any other cell type, scientists hope they may one day be used to help replace damaged or missing material in the brain, heart and immune system. The method for removing them from embryos has created a national political debate over ethics.

Hidden Stem Cells

Adult stem cells, in contrast, are hidden in tiny numbers inside developed organs. They grow into other cell types only when the body needs them to replace or help repair the body part they're linked to. As a result, some stem cell experts say the adult cells are unlikely to provide treatments for complex disorders such as Parkinson's.

Amniotic cells may be ``one more alternative among the cells that can be used for this kind of research,'' said Anthony Atala, the lead researcher, in a Jan. 5 telephone interview. ``Everything we have tried to date, we have been able to do.''

The study was published online yesterday in the journal Nature Biotechnology. Atala is director of the Wake Forest Institute for Regenerative Medicine in Winston-Salem, North Carolina.

Rolling Back Limits

Companies including Geron Corp. and Advanced Cell Technology Inc. are developing treatments from human embryonic stem cells. Democrats are preparing to introduce legislation that will roll back limits on research funding for embryonic stem cells that President George W. Bush set in 2001 because of reluctance to allow the destruction of embryos.

Atala said he discovered amniotic cells seven years ago and has been studying them ever since to make sure that they're ``pluripotent,'' meaning that they can form a wider variety of cell types than adult stem cells. The amniotic stem cells can also double in number every 36 hours, dividing at least 250 times without mutating, while aging-related structures on their chromosomes, called telomeres, remain intact, he said.

Using naturally occurring body chemicals called growth factors, Atala stimulated the amniotic cells to make brain cells. When he injected them into the brain-diseased mice, they connected with other brain cells and appeared ready to function.

Don't Form Tumors

One major difference is that, unlike embryonic stem cells, the amniotic cells don't form tumors, called teratomas, that contain a variety of cell types, Atala said. That may offer an advantage if the cells turn out to be able to regenerate tissues that are lost in Parkinson's, Alzheimer's, diabetes, and other disorders, he said.

``It makes sense because the cells are further down the line in development,'' he said. ``You don't see fetuses getting tumors.''

Lack of ability to form teratomas is an important distinction from embryonic stem cells, said Leonard Zon, a Harvard Medical School stem cell researcher who also works at Children's. Embryonic stem cells are unique in that they just one of them can reconstitute an entire organism, he said.

Atala's cells may be a form of adult stem cell called mesenchymal cells, Zon said. Aastrom Biosciences Inc., based in Ann Arbor, Michigan, and other companies work with that cell type.

`No Evidence'

There's no evidence that research on the amniotic cells is a replacement for work on embryonic stem cells, which have shown the ability to replace cells throughout the body, said Eve Herold, director of public policy research and education at the Genetics Policy Institute, a Washington-based nonprofit research advocacy group.

``There is only one `card-carrying' pluripotent human embryonic stem cell,'' she said in a statement distributed by PR Newswire. ``Patients demanding cures must reject any attempted spin on this story claiming the work with fetal cells is an actual alternative to current embryonic stem cell research.''

Several laboratories have already used amniotic cells to make muscle, bone, cartilage and tendons, as well as heart, nerve and liver cells, said Dario Fauza, a Harvard Medical School professor of surgery at Children's Hospital in Boston, in a telephone interview today. Fauza said he proposed using the cells for treatment in 2001 and has been trying to grow tissues from them to perform surgery on newborns and fetuses.

The study holds ``in-depth information on the previously known fact that the amniotic fluid holds unique stem cell populations,'' Fauza said in an e-mail today. ``The fact that different types of stem cells are present in the amniotic fluid has been known since the early nineties, though they certainly need to be better defined.''

Replicate the Work

Many laboratories have claimed to have found cells outside the embryo that share the ability to become a wide variety of tissues, said Jeanne Loring, a researcher at the Burnham Institute in La Jolla, California, who has been working with stem cells for 20 years. Other laboratories will have to replicate the work with the amniotic cells before it's accepted, she said.

``We're all very cautious because people have been wrong so many times,'' she said Jan. 5 in a telephone interview.

Laboratories across the U.S. and Europe are working with amniotic stem cells, Atala said. They normally constitute about 1 percent of cells in the amniotic fluid and, with 4.5 million births annually in the U.S. alone, could be obtained by many more laboratories, he said.

If further experiments show that the amniotic stem cells can make tissues that will function in human nerves, liver, heart or other organs, banks of them could be established to provide treatment, he said.

``These are still very early days,'' Harvard's Chien said. ``A lot of steps have to be taken before we know that these cells are useful and can be produced in sufficient quantities, but this is the beginning of a different approach.''