"Pluripotent" stem cells—which have the potential to mature into almost any cell in the body—are being widely studied for their role in treating a vast array of human diseases and for generating cells and tissues for transplantation.
Now, a team of Scripps Research Institute scientists has created a quality control diagnostic test that will make it much easier for researchers to determine whether their cell lines are normal pluripotent cells.
The study was published in an online version of Nature Methods on March 6, 2011.
"Many scientists are unhappy with the current gold standard for testing for pluripotency, called the teratoma assay," said Scripps Research molecular biologist Jeanne Loring, principal investigator of the study. "The teratoma assay requires animal testing and a time span of six to eight weeks before scientists can prove that they have a pluripotent stem cell line. In addition, this method is technically challenging and difficult to standardize."
The new test, called "PluriTest," meets the need for a cost-effective, accurate, animal-free alternative to the teratoma assay for assessing pluripotency. Using microarray technology, which enables the simultaneous analysis of thousands of different DNA sequences, the Scripps Research team created a large database of information about all the genes that are active in hundreds of normal human embryonic and induced pluripotent stem cells and a variety of non-pluripotent cell lines. For PluriTest, this database was used to create a detailed molecular model of a normal pluripotent stem cell line.
"Unlike diagnostic tests that use small sets of biomarkers to examine cells, the molecular model approach uses all of the thousands of pieces of information in a microarray," Loring said. "This results in a diagnostic test with remarkable sensitivity and specificity." Scientists upload raw data straight from a single microarray analysis to the PluriTest website and learn within 10 minutes whether their cell line is pluripotent.
An additional feature of the PluriTest diagnostic test is that it can show whether a cell that is pluripotent is different in some way from the normal model pluripotent cell line. For example, a "novelty score" generated by the software may indicate that the pluripotent cells have genomic aberrations such as extra copies of genes or chromosomes. This feature would alert the researcher to do additional analysis on the cells to determine what is causing the abnormality.
A first author of the study, Franz-Josef Mueller, said, "Scientists are making new induced pluripotent stem cell lines at a rapid pace to understand human disease, test new drugs, and develop regenerative therapies. Thousands of induced pluripotent stem cell lines have already been generated and soon there will be many more thousands. PluriTest is designed to enable the growth of this technology."
First authors of the paper, "A bioinformatic assay for pluripotency in human cells," are Mueller of Zentrum fur Integrative Psychiatrie (Kiel, Germany) and Bernhard M. Schuldt of Rheinisch-Westfalische Technische Hoschschule Aachen (Aachen, Germany). In addition to Loring, Mueller, and Schuldt, authors of the study included Roy Williams of the Sanford-Burnham Medical Research Institute, Dylan Mason (an independent consultant), Gulsah Altun of Scripps Research, Eirini P. Papapetrou of Memorial Sloan-Kettering Cancer Center, Sandra Danner of Fraunhofer Research Institution for Marine Biotechnology (Lubeck, Germany), Johanna E. Goldmann of Scripps Research and Freie Universitat (Berlin, Germany), Arne Herbst and Josef B. Aldenhoff of Zentrum fur Integrative Psychiatrie, Nils O. Schmidt of University of University Medical Center Hamburg-Eppendorf, and Louise C. Laurent of Rheinisch-Westfalische Technische Hoschschule Aachen and the University of California, San Diego.
The study was supported by the California Institute for Regenerative Medicine, the National Institutes of Health, the Bill and Melinda Gates Foundation, the Esther O'Keeffe Foundation, New York State Stem Cell Science, Bayer Technology Services GmbH, the Deutsche Forschungsgemeinschaft, an Else-Kröner Fresenius Stiftung fellowship.
About The Scripps Research Institute
The Scripps Research Institute is one of the world's largest independent, non-profit biomedical research organizations. Headquartered in La Jolla, California, Scripps Research is internationally recognized for its discoveries in immunology, molecular and cellular biology, chemistry, neuroscience, and synthetic vaccine development, as well as autoimmune, cardiovascular, and infectious disease. The institute also includes a campus in Jupiter, Florida, where scientists focus on basic biomedical science, drug discovery, and technology development. Scripps Research currently employs approximately 3,000 scientists, staff, postdoctoral fellows, and graduate students on its two campuses. The institute's graduate program, which awards Ph.D. degrees in biology and chemistry, is ranked among the top ten such programs in the nation. For more information, see www.scripps.edu.
Mika Ono | EurekAlert!
What happens in the cell nucleus after fertilization
06.12.2016 | Helmholtz Zentrum München - Deutsches Forschungszentrum für Gesundheit und Umwelt
Researchers uncover protein-based “cancer signature”
05.12.2016 | Universität Basel
In recent years, lasers with ultrashort pulses (USP) down to the femtosecond range have become established on an industrial scale. They could advance some applications with the much-lauded “cold ablation” – if that meant they would then achieve more throughput. A new generation of process engineering that will address this issue in particular will be discussed at the “4th UKP Workshop – Ultrafast Laser Technology” in April 2017.
Even back in the 1990s, scientists were comparing materials processing with nanosecond, picosecond and femtosesecond pulses. The result was surprising:...
Have you ever wondered how you see the world? Vision is about photons of light, which are packets of energy, interacting with the atoms or molecules in what...
A multi-institutional research collaboration has created a novel approach for fabricating three-dimensional micro-optics through the shape-defined formation of porous silicon (PSi), with broad impacts in integrated optoelectronics, imaging, and photovoltaics.
Working with colleagues at Stanford and The Dow Chemical Company, researchers at the University of Illinois at Urbana-Champaign fabricated 3-D birefringent...
In experiments with magnetic atoms conducted at extremely low temperatures, scientists have demonstrated a unique phase of matter: The atoms form a new type of quantum liquid or quantum droplet state. These so called quantum droplets may preserve their form in absence of external confinement because of quantum effects. The joint team of experimental physicists from Innsbruck and theoretical physicists from Hannover report on their findings in the journal Physical Review X.
“Our Quantum droplets are in the gas phase but they still drop like a rock,” explains experimental physicist Francesca Ferlaino when talking about the...
The Max Planck Institute for Physics (MPP) is opening up a new research field. A workshop from November 21 - 22, 2016 will mark the start of activities for an innovative axion experiment. Axions are still only purely hypothetical particles. Their detection could solve two fundamental problems in particle physics: What dark matter consists of and why it has not yet been possible to directly observe a CP violation for the strong interaction.
The “MADMAX” project is the MPP’s commitment to axion research. Axions are so far only a theoretical prediction and are difficult to detect: on the one hand,...
16.11.2016 | Event News
01.11.2016 | Event News
14.10.2016 | Event News
06.12.2016 | Materials Sciences
06.12.2016 | Medical Engineering
06.12.2016 | Power and Electrical Engineering