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