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EurekAlert
Public release date: 18-Mar-2003
Contact: Joanna Downer
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Johns Hopkins Medical Institutions
Scientists find new way to grow human embryonic stem cells

Johns Hopkins scientists have discovered that primitive human
embryonic stem (ES) cells, temperamental in the lab, can be grown
with the help of special cells from bone marrow, offering an easily
obtained and well-studied source of human cells to nurture the human
ES cells as they divide. First announced in 1998, human embryonic
stem cells are usually grown in the lab on a "feeder layer" of mouse
cells. Feeder cells send as yet unknown signals to the primitive
human ES cells, preventing them from turning into more "grown-up"
cell types, such as bone, fat, or brain cells.

The Johns Hopkins team found that human marrow stromal cells can also
act as feeder cells for human ES cells, letting them divide without
differentiating. Tests show that the human ES cells, obtained from
the University of Wisconsin, retain their primitive nature when grown
on the stromal cells, the scientists report in the March issue of the
journal Stem Cells.

"After eight months of dividing under these conditions, the human
embryonic stem cells still look and act just like the originals,"
says Linzhao Cheng, Ph.D., assistant professor of oncology at the
Johns Hopkins Kimmel Cancer Center. "Marrow stromal cells co-exist
with blood-forming stem cells in bone marrow and support their growth
in the lab, but we were surprised they could fully replace mouse
cells in supporting more primitive ES cells."

Marrow stromal cells are also known as mesenchymal stem cells, which
are capable naturally of becoming fat, cartilage and bone. Some
animal experiments have suggested that mesenchymal stem cells can be
manipulated to form other types of cells in laboratory dishes, but
that is still being evaluated.

One concern with using mouse cells as the feeder layer for human ES
cells is that an animal virus might be passed to people if the human
ES cells someday are used to treat patients. Although such
applications are in the fairly distant future, if human cells can act
as feeders, new lines of human ES cells could be created without
exposing them to mouse cells.

"When it is time to create new stem cell lines, this issue will be
very important," says Cheng. "Our results together with others' show
that it should be possible to establish new stem cell lines without
using mouse cells or proteins."

Late last year, scientists in Singapore reported using human cells --
one set from fetuses, one from the reproductive tract of women -- as
feeder cells to grow human ES cells in the lab. But the cells from
adult bone marrow have some distinct advantages, says Cheng.
"Marrow stromal cells don't carry the ethical baggage of the abortion
debate, they are routinely and easily obtained, and scientists
already know a lot about them, including how to dramatically expand
their numbers in the lab," says Cheng. "Scientifically, using a
variety of human cells to support the growth of human embryonic stem
cells could speed the hunt for the signals that keep the primitive
cells from changing. If that happens, we might not need any feeder
cells at all."

The researchers found that, at first, the human embryonic stem cells
didn't divide as rapidly on the human marrow stromal cells as on the
mouse cells. After one week, however, the cells adapted, grew well,
and still had the right shape, behavior and protein markers (Oct-4
and SSEA-4, etc.) characteristic of human ES cells, says Cheng.
Numerous hurdles remain before embryonic stem cells -- or cells
derived from them -- could be useful in treating conditions like
Parkinson's disease or diabetes. In fact, basic understanding of
these cells is still quite limited, including what makes them able to
turn into any of the body's cell types, and what keeps them from
doing so at the drop of a hat, notes Cheng.

"Mouse embryonic stem cells have been studied for more than 20
years," he says. "We know what signals keep them from
differentiating, we know the whole pathway. But human embryonic stem
cells have only been studied for the last five years, and only in the
last year has the investigation expanded to multiple labs in the
United States and elsewhere. What we've learned so far shows human
and mouse ES cells to be quite different. The more ways we have to
study human ES cells, the faster we can learn."

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SOURCE: EurekAlert
http://www.eurekalert.org/pub_releases/2003-03/jhmi-sfn031803.php

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