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THURSDAY, April 5 (HealthDay News) — Developing stem cell lines
that don’t have cells that potentially grow into tumors has been one of
the biggest challenges for stem cell therapies.

But researchers from the Children’s Hospital of Philadelphia have
generated a new line of stem cells that may solve that problem, at least
for stem cells destined for the digestive system or possibly the
lungs.

“The most significant use short-term will be for disease modeling.
We’ve had to rely on mouse models, but we’re different than mice. A model
with human cells could be very powerful,” said the study’s senior author,
Paul Gadue, an assistant professor in the department of pathology and
laboratory medicine at the hospital’s Center for Cellular and Molecular
Therapeutics.

In the far future, he added, these stem cells could potentially be
used as therapies for diseases such as diabetes or liver disease.

For the current research, the scientists used embryonic stem cells and
induced pluripotent stem cells. Embryonic stem cells are derived from
human embryos, often unused embryos from fertility treatments that are
donated for research. Induced pluripotent stem cells are genetically
engineered from other human cells, such as skin cells or blood cells. Both
of these stem cell types can give rise to tumors.

“One of the big issues that’s critical when you think about potentially
transplanting embryonic stem cells or induced pluripotent stem cells is
that you have to make sure there are no undifferentiated cells in that
batch, because undifferentiated cells can form tumors called teratomas,”
said Gadue.

By stalling the development of these cells at what’s called the
endodermal stage, the researchers found that the cells no longer created
teratomas. The endoderm is the innermost layer of cells found in an early
embryo that eventually develop into the lining of the digestive and
respiratory tract.

These cells are then known as endodermal progenitor cells, and they
have nearly unlimited growth potential in the lab, according to the
authors.

But, delaying the cells at the endodermal stage does limit the type of
cell they can later become. Endodermal progenitor cells can only become
cells found in the digestive tract, such as intestinal, liver or
pancreatic cells, and possibly lung cells, Gadue said.

It’s as if the initial stem cells are college freshmen undecided about
what course of study they want to pursue. At this point, they can
essentially choose any career. For stem cells, that means some choose to
become tumors.

However, Gadue and his colleagues found a way to guide the cells to the
school of study that might be right for them, such as a school of
engineering or a school of art. And, for stem cells, that means the choice
no longer includes becoming a teratoma. But, that also means that the
cells’ pathways are more limited, like an engineering major who chooses a
subspecialty of mechanical engineering, but can no longer choose art.

Of course, while creating a stem cell line that doesn’t produce
teratomas is important, it’s also important that cells in that line grow
up (differentiate) to become other cells. And Gadue’s team was able to
create pancreatic beta cells that could produce some insulin. Beta cells
are the cells that are damaged or destroyed in people with diabetes.

The investigators found that in the lab, the newly created beta cells
produced insulin after being exposed to glucose (sugar), a function that
is absent or impaired in people with diabetes. However, the cells didn’t
achieve full function, producing only about 20 percent of the expected
insulin.

Juan Dominguez-Bendala, director of stem cell development for
translation research at the Diabetes Research Institute in Hollywood,
Fla., said that the 20 percent function isn’t much different than what’s
been seen in other studies, and that getting beta cells to mature fully in
the lab is very difficult. He added that beta cells will often complete
maturation once they’ve been transplanted.

But overall, Dominguez-Bendala said, “this [research] presents two
major advantages over embryonic stem cells. First, by having this
‘intermediate’ population, we are restricting the differentiation options
of the stem cells. For applications such as liver diseases or diabetes,
these cells will readily become [liver cells] or beta cells, without
unwanted byproducts such as [nerve or heart cells].” And second and more
importantly, he said, they don’t pose the risk of forming tumors.

“If independently confirmed, this approach could certainly be of great
potential to design safer and more efficient differentiation protocols for
the treatment of diabetes and liver diseases, among other conditions,”
Dominguez-Bendala added.

Albert Hwa, scientific program manager of cure therapies at the
Juvenile Diabetes Research Foundation, called the new research “very
interesting and encouraging because they don’t see teratomas.” He also
agreed that the functionality of the beta cell could be further
optimized.

“This was a first try with this protocol. The function of these cells
seems very promising as well,” said Hwa.

Hwa also said the findings need to be replicated, but that he could see
such stem cells being used for disease modeling.

However, Hwa added, a therapy for type 1 diabetes from this stem cell
line is less likely “until we can look at this process consistently in a
large scale. For the [U.S. Food and Drug Administration], you have to show
data that you can consistently produce the same product.”

Results of the study are published in the April 6 issue of the journal
Cell/Stem Cell.

More information

Learn more about stem cells from the U.S. National
Institutes of Health.