Chemicals
in pharmaceutical drugs can obviously save lives. But as more and
stronger chemicals have been introduced, our basic knowledge of the
broader health impact of all these chemicals has not kept up with the
rapid pace of innovation. There is exceptionally little information on
how chemicals in our drugs and also in the environment around us,
including on the food we eat, impact some of the most important cells in
our body: stem cells. Without basic knowledge and tests on the impact
of chemicals on our stem cells, we may be unwittingly damaging essential
regenerative functions in our body.
Bioengineers
at Rensselaer Polytechnic Institute and the University of California,
Berkeley, have been awarded a more than $2 million grant from the
National Institutes of Health (NIH) to study how chemicals in drugs and
our environment impact our stem cells.
Leading
the research effort for Rensselaer is Jonathan Dordick, director of the
Center for Biotechnology and Interdisciplinary Studies (CBIS) and the
Howard P. Isermann ’42 Professor of Chemical and Biological Engineering.
Dordick is co-principal investigator on the grant with David Schaffer,
professor of chemical and biomolecular engineering and co-director of
the Berkeley Stem Cell Center at the University of California, Berkeley.
The
researchers hypothesize that stem cells, which are essential for the
replacement of dead and damaged tissues in the body, react in
fundamentally different ways to chemicals than other cells in the body.
The grant will allow them to study the impacts of known chemical
compounds on adult stem cells, providing the most substantive
information to date on how many of the chemicals used every day around
the world in drugs, pesticides, and other products impact stem cells.
The work also will seek to develop a new predictive safety screening
tool that manufacturers can use to test the toxicity of new chemical
compounds on stem cells before their drug or other product reaches the
market. The test will be done without the use of animals and at speeds
far faster than current tests.
“When
you look at the toxicity of drugs or other chemicals in our
environment, you want to understand the response that all the different
cells in the body have to that compound,” Dordick said. “Most current
toxicity screens used by manufacturers focus on a narrow range of cell
types. Stem cells typically have not been included, although there is
now a rapidly growing interest in the pharmaceutical industry in using
such cells. This greatly limits our understanding of what a new drug or
chemical will have on the body. Vast amounts of money are wasted on the
failed development process and, more importantly, people’s health could
be unknowingly put at risk.”
Dordick notes that this paradigm may be proving a reality in the case of many cancer drugs.
“Chemotherapy
is pretty effective at killing cancer cells, but it also damages other
cell types in the process,” he said. “In fact, when some of these
treatments are complete, the ability of certain organs to regenerate is
compromised, which may be due to selective damage to such organs’ stem
cells. With this grant, we hope to better understand this to help weigh
the pros and cons of different treatments.”
To
perform the research, the team will utilize what is known as
lab-on-a-chip technology. The technology allows for the swift testing of
thousands of different chemicals on the surface of one simple, small
chip. The chip used in the work is similar in appearance to a
traditional glass microscope slide. Its specialized surface includes
hundreds of microscale spots of stem cell cultures. Different chemicals
can then be added to each of these culture spots. The stem cells will
then be analyzed for their reaction. In this manner, hundreds of
different chemicals, including drugs and drug combinations, can be
tested on a single chip. The technology also eliminates the need for
animals in the toxicology testing. The stem cells used in the study are
human adult neural stem cells and adult mesenchymal stem cells (which
are grown in our connective tissue). The work will provide a baseline of
fundamental knowledge on how stem cells are impacted by the chemicals
around us.
The
ultimate goal of the research is to develop a high-throughput and
inexpensive system that manufacturers can use to quickly screen
thousands of chemicals for their effects on stem cells, according to
Dordick.
“One
of the goals would be that we would add a stem cell screening component
to the safety testing of a pharmaceutical candidate or to the
assessment of the health effect of a chemical in the environment, say on
our food,” he said. “This would give us a much broader understanding of
how the human body will respond to these chemical compounds.”
The
work is an extension of Dordick’s previous work conducted in a
long-standing collaboration with Douglas Clark, the Warren and Katharine
Schlinger Distinguished Professor and Chair, Department of Chemical and
Biomolecular Engineering at the University of California, Berkeley. He
is co-investigator in the current project, to develop inexpensive
high-throughput toxicology tests and reduce the use of animals in such
testing.
Information on their previous research
The
grant is over a four-year period. Dordick, Schaffer, and Clark will be
joined in the research by Robert Linhardt, Ann and John H. Broadbent Jr.
’59 Senior Constellation Professor of Biocatalysis and Metabolic
Engineering at Rensselaer.