To do that, SCR&Tox researchers have been working on differentiating iPS cells into the five mature tissue types the project studies. Rosas
says they’ve confronted many of the same problems other investigators
have had, especially the tendency of stem cells to retain immature characteristics even after differentiation. Nonetheless, SCR& Tox-developed
assays will soon find their way into industry laboratories for testing and
validation, and Rosas hopes regulatory agencies will begin accepting
stem cell-based toxicity data for cosmetics within a few years.
Another large European research project, StemBANCC, is also
working to improve the use of stem cells in toxicology assays. While
SCR&Tox researchers are developing general-purpose toxicology assays based on iPS cells derived from healthy volunteers, StemBANCC
scientists are focusing on iPS cells derived from 500 patients with various diseases. These disease-specific cells will form the basis for a new
generation of drug development assays, including toxicological tests.
“The generation of induced pluripotent cells is just a technical goal.
More important [is] to then differentiate them into a cell type that is
relevant for a disease ... and then try to understand the disease in a dish,”
says Martin Graf, head of the stem cell platform at Hoffmann-La
Roche in Basel, Switzerland and one of the leaders of the StemBANCC
Besides cell samples, StemBANCC will also collect detailed clinical
data from the patients. “One of the big things about this project is the
depth of the clinical phenotyping that we’re going to be doing on these
patients, I think the real value of the cell lines subsequently is having
that phenotyping information,” says Zameel Cader, academic director
of StemBANCC and a professor of clinical neurosciences at Nuffield
College in Oxford, United Kingdom. Besides a diagnosis and history,
each StemBANCC line will come with extensive data from diagnostic
tests characterizing the patient’s disease progression, treatments, and
Ultimately, the project seeks to give pharmaceutical researchers
THIS IS YOUR BRAIN ON A CHIP
realistic laboratory models of individual patients, yielding more reliable
predictions of a new drug’s efficacy and toxicity long before it reaches
the clinic. “I think in vitro toxicology using patient-derived material is
really the first step towards trying to address the fall-off in drugs during
their development,” says Cader.
Other researchers are taking the patient-in-a-dish concept a step further by trying to grow multiple tissue types together in organ-like 3-D
cultures. Luc Stoppini, professor of tissue engineering at the
University of Applied Sciences of Western Switzerland in Delemont,
Switzerland, began such a project after an initial disappointment with
conventional stem cell culture. “People were claiming that they had
[stem cell-derived] neurons, because they were expressing beta-3 tu-bulin which is one of the markers of neurons, but when I looked at
them they were like fibroblasts, not really differentiating with axons,
neurites, and synapses,” says Stoppini.
As a neurobiologist, Stoppini wanted a more realistic neuronal
system. Allowing the stem cell-derived “neurons” to grow in a 3-D
culture system caused them to develop more neuronal shapes, and
the cells also began transmitting electrical signals. The trick was
to let the 3-D cultures grow much longer than traditional flat cultures; the neurons often continue developing for several months.
“The message here is that we really need time to get human neuron
function,” says Stoppini. He adds that this slow development may
make it hard to scale some assays to the high throughput needs of
Nonetheless, the payoff for getting such a system working could be
huge. In particular, Stoppini says the long-term cultures can develop
some of the non-neuronal cell types that are crucial for normal nervous system functions, such as astrocytes and oligodendrocytes. His
team can now derive these miniature brains from both embryonic and
iPs cells, raising the possibility of mimicking specific neural diseases
with patient-derived cells.
The investigators have also taken the process a step further, growing
3-D brain cultures on microfluidic chips dotted with electrical sensors.
Microcapillaries bring fresh nutrients to the culture while the sensors
record electrical activity.
Stoppini is also connecting the brain chip to other stem cell-derived
microfluidic organ cultures. Future pharmaceutical researchers might
be able to feed an experimental drug into a patient-derived intestine,
which would then deliver its metabolites through a vascular system to a
miniature liver, finally affecting the activity of an in vitro brain. “At the
end of the day we expect to have what we call the petri dish of the 21st
century, that’s to have a culture embedded in a biochip where all the
biosensors ... are integrated,” says Stoppini.
The latest iteration of the technology also includes a Wi-Fi transmitter,
so researchers can monitor the system without even opening the
incubator. Stoppini adds that, “it’s an extraordinary period that’s opened
new avenues of research by combining the biological tools [with
electronics] ... so we can really have some glimpse of how these things
GE Life Sciences
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Life Science Technologies
University of Applied Sciences
Alan Dove is a science writer and editor based in Massachusetts.
“At the end of the day we expect to have what we
call the petri dish of the 21st century, that’s to have
a culture embedded in a biochip where all the