TTP Labtech, Phenotypic Screening - 26

PHENOTYPIC SCREENING an e-Book Series Novel 3D Cell Culture Systems

cell types. These same factors are as important in
studying drug responsiveness in cultured microtissue
constructs, as in evaluating the efficacy of
therapeutic strategies targeting tumors.
In the latter case, the ability to simulate the
microtumor environment, communication between
tumor cells, the effects of the tumor stroma
environment, and the interaction of tumor cells
with other surrounding cell types such as epithelial
cells or fibroblasts, can enhance the ability to study
mechanisms of tumorigenesis, cell migration and
invasion, and metastasis.
One of the main and ongoing challenges has
been to develop in vitro 3D cell culture systems that
are compatible with industrial-scale applications
and are readily automatable for high-throughput
screening assays.
Jens Kelm, Ph.D., CSO and co-founder of
InSphero, described three 3D cell culture methods
that are currently most broadly accepted in the
industry: cell constructs embedded in hydrogels;
cells grown in scaffolds; and cellular self-assembly
leading to spheroid formation. InSphero's approach
26 | GENengnews.com

leads to the formation of scaffold-free 3D multicellular spheroids in a 96-well format. The company's
GravityPLUS™ technology automates the classic
hanging drop methodology, in which cells in hanging
drops of culture media descend and assemble into
microtissue spheroids without the need for any
support matrices or contact with any surfaces.
"We have exploited the versatility of hanging
drop production by uncoupling the generation of
microtissues from downstream applications," said
Dr. Kelm. "This was the creation of our platform,
producing very uniform spheroids or microtissues
while also allowing for compound treatments,
microscopic analysis and assays, to get the best of
both worlds!"
In his presentation at the SMi meeting, Dr. Kelm
described the availability of an increasing variety of
model systems available to industry and the research
community for testing the safety, toxicity, and efficacy
of drug compounds in in vitro systems and minimizing
the need for animal testing. The demand for good
in vitro model systems for screening extends beyond
the pharmaceutical industry, with safety assessment

of chemicals and other compounds important for
the chemicals and cosmetics industries as well.
"We are using reporter systems that are
allowing us to perform target validation in 3D
model systems," said Dr. Kelm. This has revealed
sometimes substantial differences in the effects
of drugs on microtissues versus cells grown in
monolayer systems, and in particular in models
of tumor growth and proliferation.
One goal going forward is standardization.
It would be convenient, for example, to have
standardized 3D liver and cardiac model systems
available for safety testing. "It is important to
generate comparable results, to test on the same
model and be able to compare results over years
and across drugs," added Dr. Kelm.
Dr. Kelm foresees continued progress in
mimicking interconnected, complex tissue constructs
in functional living tissue models-so-called bodyon-a-chip concepts. Two consortia, one in the United
States and one in Europe, are working on this
concept. InSphero is participating in the European
project, in which the different tissue types are


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TTP Labtech, Phenotypic Screening

Table of Contents for the Digital Edition of TTP Labtech, Phenotypic Screening

Contents
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