TTP Labtech, Phenotypic Screening - 24

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

large-scale screening campaigns and of more
widespread adoption of the technology, in Dr.
Pardo's view.
One of the main advantages of the 3D collagen
assay and of 3D culture systems in general is the ability
to do co-cultures, noted Dr. Pardo, thereby more closely
mimicking the in vivo environment and enabling the
introduction of cells capable of producing growth
factors and other natural molecules to support the
health and viability of the cultured cells.
An Automatable,
Scaffoldless System
At Trinity College in Dublin, Anthony Davies,
Ph.D., director of the high-content facility, and
colleagues developed a novel liquid scaffold system
that permits 3D cell culture and subsequent harvesting
of the cells. The researchers designed the system
to be compatible with essentially any automated
liquid-handling and high-throughput screening
system, as well as high-content screening and
image-analysis technology.
"Unlike any other 3D assay systems currently
24 | GENengnews.com

Human Brain Tissue Grown in Test Tubes
Researchers from the Institute of Molecular Biotechnology (IMBA) of the Austrian Academy of
Sciences report the development of human brain tissue in a 3D cell-culture system. Their technique,
which is discussed in an article last month in Nature ("Cerebral organoids model human brain
development and microcephaly"), permits pluripotent stem cells to develop into cerebral organoids,
or "mini brains," that consist of several discrete brain regions.
"Our goal was to create a model system of the human brain," said J├╝rgen Knoblich, Ph.D., IMBA's
deputy scientific director during a press conference.
Intrinsic cues from the stem cells guided the development toward different interdependent brain
tissues. Using the mini brains, the scientists were able to model the development of a human neuronal
disorder (i.e., microcephaly) and identify its origin.
"A normal developing brain has a stem cell population that undergoes rounds of division at specific
times to make more stem cells and eventually neurons," noted Dr. Lancaster. "But the microcephalic
patient-derived stem cells made neurons too early in the process. This led to a depletion of the stem
cell population, which resulted in fewer neurons being made."
Putting it another way, Dr. Knoblich explained that this finding led to the hypothesis that, during brain
development of patients with microcephaly, the neural differentiation happens prematurely at the expense
of stem and progenitor cells, which would otherwise contribute to a more pronounced growth in brain size.
"Further experiments also revealed that a change in the direction in which the stem cells divide might be
causal for the disorder," he continued.
The new method offers great potential for establishing model systems for human brain disorders,
according to the researchers. Such models are urgently needed, as the commonly used animal models
are of considerably lower complexity and often do not adequately recapitulate the human disease. n


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TTP Labtech, Phenotypic Screening

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