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A polarized light micrograph (top view) of human embryonic stem cells cultured for three days on a Matrigel-coated film of liquid crystal hosted within a small grid. The bright regions in the image correspond to the regions where the stem cells have grown. Dark regions are void of cells. As the human embryonic stem cells grow on the liquid crystal, they reorganize a thin layer of proteins (called Matrigel) that separates the cells from the liquid crystal, thereby leading to patterned orientations of the liquid crystal. Depending on its local orientation, the liquid crystal can transmit light or block it, giving rise to dark and bright regions in the image. [2-MB high-resolution image] (large image)
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Liquid crystals, the same phase-shifting materials used to display
information on cell phones, monitors and other electronic equipment, can
also be used to report in real time on the differentiation of embryonic
stem cells.
Differentiation is the process by which embryonic stem cells gradually
turn into function-specific types of adult cells or so-called “cell
lineages” including skin, heart or brain.
The main challenge facing stem cell research is that of guiding
differentiation along these well-defined, controlled lineages. Stem
cells grown in the laboratory tend to differentiate in an uncontrolled
manner, resulting in a mixture of cells of little medical use.
Now, UW-Madison researchers at the NSF-funded
Materials Research Science and Engineering Center (MRSEC)
have shown that by straining mechanically
the cells as they grow, it is possible to reduce significantly and
almost eliminate the uncontrolled differentiation of stem cells.
In an article in the March issue of Advanced Functional Materials, the
team reports on a liquid crystal-based cell culture system that promises
new ways of achieving real-time control over interactions between
synthetic materials and human embryonic stem cells, including the
possibility of straining embryonic stem cells as they grow.
“Stem cells tend to be smaller and have a slightly more compact shape
than the differentiated cells,” says
Chemical and Biological Engineering
Assistant Professor
Sean Palecek.
“Differentiated cells appear to be
much more spread and they appear to exert different levels of force on
the matrix in which they are grown. That force can be read to a liquid
crystal. Through simple changes of liquid crystal texture and color, our
cell culture system is able to report, in real time, the cell
interactions with the underlying support on which they are grown.”
Currently, researchers have several methods of monitoring cell
differentiation. The easiest, says
Palecek,
is to just look at the cells
and use cell morphology as a cue. A more accurate method uses molecular
markers. Antibodies are placed against these markers to determine if
they bind to the cell. That system, while more accurate, does not
provide real time data and cells often have to be killed in order to
analyze the markers.
“This newly devised cell culture system enables a new paradigm in stem
cell research,” says
Chemical and Biological Engineering
Professor and
MRSEC
Director
Juan de Pablo.
“Ultimately, we hope to use liquid
crystalline materials to transmit desired sets of physical and chemical
cues to stem cells so as to control their differentiation, as well as
report back specific responses of the cells or tissue.
This research is also significant as an example of our unique effort to
integrate advanced materials engineering and embryonic stem cell
research, an effort that will help accelerate the rate at which the
benefits of stem-cell based therapies are brought to society.”
In addition to
Palecek
and
de Pablo,
authors of the paper include former
post-doctoral researcher Nathan Lockwood, Graduate Student Jeff Mohr,
Researcher Lin Ji, School of Veterinary Medicine (Ophthalmology) and
Biomedical Engineering
Professor
Christopher Murphy,
and
Chemical and Biological Engineering
Professor
Nicholas Abbott.
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Copyright 2006 The Board of Regents of the University of Wisconsin System
Date last modified: 06-Mar-2006
Date created: 06-Mar-2006
Content By: perspective@engr.wisc.edu
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