SCIENTISTS MAKE STRIDES TOWARD FIXING INFANT HEARTS

Rice University, Texas Children’s Hospital researchers derive vessel-forming stem cells from amniotic fluid

Researchers at Rice University and Texas Children’s Hospital have turned stem cells from amniotic fluid
into cells that form blood vessels. Their success offers hope that such
stem cells may be used to grow tissue patches to repair infant hearts.

“We want to come up with technology to replace defective tissue
with beating heart tissue made from stem cells sloughed off by the
infant into the amniotic fluid,” said Rice bioengineer Jeffrey Jacot,
who led the study. “Our findings serve as proof of principle that stem
cells from amniotic fluid have the potential to be used for such
purposes.”

The results were published online by the journal Tissue Engineering Part A. The research was conducted at Texas Children’s Hospital.

According to the American Heart Association, about 32,000
infants a year in the United States are born with congenital heart
defects, 10,000 of which either result in death or require some sort of
surgical intervention before they’re a year old.

Jacot, an assistant professor of bioengineering based at Rice’s BioScience Research Collaborative and director of the Pediatric Cardiac Bioengineering Laboratory at the Congenital Heart Surgery Service
at Texas Children’s Hospital, hopes to grow heart patches from the
amniotic stem cells of a fetus diagnosed in the womb with a congenital
heart defect. Because the cells would be a genetic match, there would be
no risk of rejection, he said.

“Between 60 and 80 percent of severe heart defects are caught
by ultrasound,” he said. “Ultimately, when a heart defect is diagnosed
in utero, we will extract amniotic cells. By birth, we will have made
tissue for the repair out of the infant’s own cells. The timing is
critical because the surgery needs to be done within weeks of the
infant’s birth.”

Surgeons currently use such nonbiological materials as Dacron
or Teflon, which do not contract or grow with the patient, or native
pericardium, the membrane that surrounds the heart. Pericardium
generally forms scar tissue and can only be used in the first operation.
Both solutions require further operations and raise the risk of cardiac
arrest, Jacot said.

Stem cells, the focus of both great hope and great controversy,
are the cells in every organism that differentiate into specialized
cells in the body. Stem cells drawn from human embryos are known to have
great potential for treatment of defects and disease, but research into
their use has been limited by political and other concerns, Jacot said.

That isn’t the case with cells found in amniotic fluid, he
said. Amniotic fluid is the liquid that protects and nourishes a fetus
in the womb. Fluid is sometimes taken from pregnant women through amniocentesis, but cells for the Jacot lab’s studies were drawn from women undergoing treatment for twin-twin transfusion syndrome.
“This is where two identical twins share a placenta and one is getting
more blood than the other. It’s not common,” he said, noting that Texas
Children’s is one of the few hospitals that treat the syndrome. “Part of
the general treatment is to remove fluid with the goal of saving both
lives, and that fluid is usually discarded.”

Jacot said other labs have tested amniotic fluid as a source of
stem cells with promising results. “Our work is based on five years of
work from other labs in which they’ve discovered a very small population
of amniotic stem cells – maybe one in every 10,000 – that naturally
express markers characteristic of embryonic and mesenchymal stem cells.”

Jacot and his team created a population of amniotic stem cells
through a complex process that involved extracting cells via
centrifugation and fluorescence-activated sorting. They sequestered
cells with a surface receptor, c-kit, a marker associated with stem cells.

The cells were cultured in endothelial growth media to make
them suitable for growing into a network of capillaries, Jacot said.
When the cells were placed in a bio-scaffold, a framework used for
tissue engineering, they did just that.

“Anything we make will need a blood supply,” he said. “That’s
why the first cell type we looked for is one that can form blood
vessels. We need to know we can get a capillary network throughout
tissue that we can then connect to the infant’s blood supply.”

Jacot said the cells they tested grow very fast. “We’ve done
calculations to show that, with what we get from amniocentesis, we could
more than grow an entire heart by birth,” he said. “That would be
really tough, but it gives us confidence that we will be able to quickly
grow patches of tissue outside of the body that can then be sewn
inside.”

He said construction of a functional patch is some years away,
but his lab is making progress. While embryonic cells have the most
potential for such a project, amniotic cells already show signs of an
ability to turn into heart muscle, he said.

Co-authors are graduate students Omar Benavides and Jennifer
Petsche, both of Rice; and Kenneth Moise Jr. and Anthony Johnson, now
professors at the Texas Center for Maternal and Fetal Treatment at The
University of Texas Health Science Center at Houston with appointments
at Children’s Memorial Hermann Hospital.

The research was supported by the National Institutes of
Health, the National Science Foundation Graduate Research Fellowship and
CAREER programs, the Houston-Rice Alliance for Graduate Education and
the Professoriate, the Howard Hughes Medical Institute Med into Grad
Program and the Virginia and L.E. Simmons Family Foundation.

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