ó They are present in soil, water and air, and exist in
products used daily at home, at work and in our vehicles. So
itís no surprise that many end up in our bodies.
the U.S. Environmental Protection Agency remains largely
unaware of the toxic impact of more than 80,000 commercially
used man-made chemicals on our blood, bones, joints, skin,
organs, brains and our babies.
turns out, less than 10 percent of all widely used chemicals
have been tested for toxicity and health risks, amid 500
million tons of synthetic chemicals produced annually,
Vanderbilt University reports.
the unknown health effects of so many common chemicals, the
EPA now has established three centers to develop technology to
test chemicals without using animals.
$6 million EPA grant over four years, Vanderbilt and the
University of Pittsburgh are establishing one of the centers
ó the Vanderbilt-Pittsburgh Resource for Organotypic Models
for Predictive Toxicity, or VPROMPT.
researchers already have been designing "tissue
chips" that are being adapted to test chemical impacts on
liver cells; other chips soon will go into development for
limbs and joints. The Vanderbilt team is working on similar
chips to test chemical impact on fetal-membrane and mammary
cells. One goal is an accurate and efficient determination of
a chemicalís potential to hinder limb development or cause
whole point of doing this is to reduce, replace or substitute
animal testing with a higher-fidelity system thatís
completely human ó but not a human being," said Rocky
Tuan, who holds many positions including director of the Pitt
School of Medicineís Cellular and Molecular Engineering.
"Itís human tissue on a chip."
confuse tissue chips with silicon chips used in computers.
Tissue chips comprise human-organ cells engineered from stem
cells or established cell lines used in different organ
studies that are placed in a micro-chamber or bioreactor
fitted with channels where a chemical can be introduced and
fluids can exit to allow for analysis of biological response
to potential toxins.
cell groups used in the chips actually are liver, limb,
cartilage and bone, mammary and fetal-membrane cells to be
tagged with markers that, Tuan said, may turn fluorescent red
when exposed to toxic substances causing cellular stress, or
green when the chemical is biologically benign or beneficial.
the system, the team will first apply toxic chemicals whose
impacts on cells already are known to produce the same results
in the tissue chips.
response to toxic stress, the researcher said, can be assessed
using many approaches: for example, by measuring levels of
cell calcium and metabolic changes in pH, oxygen and glucose
levels, and changes in cell or tissue shape. Investigators at
Vanderbilt are developing bioreactors and computerized devices
to analyze the cellular response to chemical exposures.
EPA has stockpiled a large number of possible chemical
suspects, but itís not humanely feasible to test all of them
on animals," said Tuan, who holds a Ph.D. in life
sciences. He said animal testing is only 50 percent predictive
of a chemicalís impact on humans.
imagine the complexity of using animals," he said.
"The cost is enormous. So with this, we have a chance of
simplifying it, and at the end of the day, when all is said
and done, it all will be automated. We will inject compounds.
For each model, if it glows red, itís bad, or if it glows
green, itís good."
the idea also could hold potential in assessing the safety of
food additives, drugs and pesticides.
research already is underway.
$5.8 million National Institutes of Health grant issued last
fall, D. Lansing Taylor, director of Pittís Drug Discovery
Institute and part of the Pitt team, has led the development
of a tissue chip involving liver cells and designed to mimic
the structure and function of the liver, for use in testing
the safety and effectiveness of drugs. He said he is adapting
that liver-chip technology to test the impact of chemicals on
is a very exciting field, and weíre in the early
stages," said Taylor, who holds a Ph.D. in cell biology.
"Thereís more to do and itís not a done deal, but
this has great promise, and weíve made great strides."
Institutes of Health director Francis S. Collins has said that
"the development of tissue chips is a remarkable marriage
of biology and engineering," with potential to test drug
treatments and serve as valuable tools for biomedical
from both universities have worked jointly in the past on
tissue-chip projects, the Pitt team offering specific
expertise needed for the project in liver, joint and limb
Tuan brings incredible expertise in the biology of limb
development and in understanding chemicals that cause defects
in development, and has been studying the process in limbs for
years and years," said M. Shane Hutson, a Vanderbilt
physics professor who serves as VPROMPT director.
Taylor and his group bring expertise and have been making
liver-on-chip models and bring expertise in using those chips
in drug discovery," he said. "That was his primary
focus before this, which parallels what EPA is interested