Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

Converting adult somatic cells to pluripotent stem cells using a single virus

09.01.2009
A single lentiviral vector of the expression of a 'stem cell cassette' dramatically boosts reprogramming efficiency and puts iPS technology one step closer toward human clinical trials

A Boston University School of Medicine-led research team has discovered a more efficient way to create induced Pluripotent Stem (iPS) cells, derived from mouse fibroblasts, by using a single virus vector instead of multiple viruses in the reprogramming process.

The result is a powerful laboratory tool and a significant step toward the application of embryonic stem cell-like cells for clinical purposes such as the regeneration of organs damaged by inherited or degenerative diseases, including emphysema, diabetes, inflammatory bowel disease, and Alzheimer's Disease.

Their research titled "iPS Cell Generation Using a Single Lentiviral Stem Cell Cassette" appears on line in the journal Stem Cells.

Prior research studies have required multiple retroviral vectors for reprogramming -- steps that depended on four different viruses to transfer genes into the cells' DNA – essentially a separate virus for each reprogramming gene (Oct4. Klf4, Sox2 and cMyc). Upon activation these genes convert the cells from their adult, differentiated status to what amounts to an embryonic-like state.

However, the high number of genomic integrations -- 15 to 20 -- that typically occurs when multiple viruses are used for reprogramming, poses a safety risk in humans, as some of these genes (i.e. cMyc) can cause cancer. In addition, the viruses can integrate in cell locations turning on potential oncogenes.

The major milestone the six-member research team, led by Gustavo Mostoslavsky, Boston University Assistant Professor of Medicine in the Gastroenterology Section, achieved was combining the four vectors into a single "stem cell cassette" containing all four genes. The cassette (named STEMCCA) is comprised of a single multicistronic mRNA encoding the four transcription factors using a combination of 2A peptide technology and an internal ribosomal entry site (IRES).

With the STEMCCA vector, the researchers were able to generate iPS cells more efficiently -- 10 times higher than previously reported studies.

"The use of a single lentiviral vector for the derivation of iPS cells will help reduce the variability in efficiency that has been observed between different laboratories, thus enabling more consistent genetic and biochemical characterizations of iPS cells and the reprogramming process," the researchers concluded.

"We believe that the specific design of the cassette together with the fact that all four genes are expressed from the same transcript could account for the high efficiency we obtained" commented Cesar A. Sommer, first author in the paper and a postdoctoral fellow at Boston University Medical School's Gastroenterology Section.

Most importantly, several iPS clones were generated with a single viral integration, a major advance compared to the multiple integrations observed in other studies.

"Now we could move forward toward the elimination of the whole cassette using recombination technologies", noted Mostoslavsky.

Darrell N. Kotton, another co-author on the paper and an Assistant Professor at Boston University Medical School's Pulmonary Section mentioned that preliminary studies already confirmed that the STEMCCA vector works with high efficiency for the reprogramming of human cells.

Ronald Rosenberg | EurekAlert!
Further information:
http://www.bu.edu

More articles from Life Sciences:

nachricht Asian dust providing key nutrients for California's giant sequoias
28.03.2017 | University of California - Riverside

nachricht Chlamydia: How bacteria take over control
28.03.2017 | Julius-Maximilians-Universität Würzburg

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

Die letzten 5 Focus-News des innovations-reports im Überblick:

Im Focus: A Challenging European Research Project to Develop New Tiny Microscopes

The Institute of Semiconductor Technology and the Institute of Physical and Theoretical Chemistry, both members of the Laboratory for Emerging Nanometrology (LENA), at Technische Universität Braunschweig are partners in a new European research project entitled ChipScope, which aims to develop a completely new and extremely small optical microscope capable of observing the interior of living cells in real time. A consortium of 7 partners from 5 countries will tackle this issue with very ambitious objectives during a four-year research program.

To demonstrate the usefulness of this new scientific tool, at the end of the project the developed chip-sized microscope will be used to observe in real-time...

Im Focus: Giant Magnetic Fields in the Universe

Astronomers from Bonn and Tautenburg in Thuringia (Germany) used the 100-m radio telescope at Effelsberg to observe several galaxy clusters. At the edges of these large accumulations of dark matter, stellar systems (galaxies), hot gas, and charged particles, they found magnetic fields that are exceptionally ordered over distances of many million light years. This makes them the most extended magnetic fields in the universe known so far.

The results will be published on March 22 in the journal „Astronomy & Astrophysics“.

Galaxy clusters are the largest gravitationally bound structures in the universe. With a typical extent of about 10 million light years, i.e. 100 times the...

Im Focus: Tracing down linear ubiquitination

Researchers at the Goethe University Frankfurt, together with partners from the University of Tübingen in Germany and Queen Mary University as well as Francis Crick Institute from London (UK) have developed a novel technology to decipher the secret ubiquitin code.

Ubiquitin is a small protein that can be linked to other cellular proteins, thereby controlling and modulating their functions. The attachment occurs in many...

Im Focus: Perovskite edges can be tuned for optoelectronic performance

Layered 2D material improves efficiency for solar cells and LEDs

In the eternal search for next generation high-efficiency solar cells and LEDs, scientists at Los Alamos National Laboratory and their partners are creating...

Im Focus: Polymer-coated silicon nanosheets as alternative to graphene: A perfect team for nanoelectronics

Silicon nanosheets are thin, two-dimensional layers with exceptional optoelectronic properties very similar to those of graphene. Albeit, the nanosheets are less stable. Now researchers at the Technical University of Munich (TUM) have, for the first time ever, produced a composite material combining silicon nanosheets and a polymer that is both UV-resistant and easy to process. This brings the scientists a significant step closer to industrial applications like flexible displays and photosensors.

Silicon nanosheets are thin, two-dimensional layers with exceptional optoelectronic properties very similar to those of graphene. Albeit, the nanosheets are...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

Event News

International Land Use Symposium ILUS 2017: Call for Abstracts and Registration open

20.03.2017 | Event News

CONNECT 2017: International congress on connective tissue

14.03.2017 | Event News

ICTM Conference: Turbine Construction between Big Data and Additive Manufacturing

07.03.2017 | Event News

 
Latest News

Researchers create artificial materials atom-by-atom

28.03.2017 | Physics and Astronomy

Researchers show p300 protein may suppress leukemia in MDS patients

28.03.2017 | Health and Medicine

Asian dust providing key nutrients for California's giant sequoias

28.03.2017 | Life Sciences

VideoLinks
B2B-VideoLinks
More VideoLinks >>>