Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

Reprogramming Human Cells Without Inserting Genes

30.07.2009
Research Team at WPI and CellThera Discovers a Way to Turn on Stem Cell Genes in Human Skin Cells Without Using Viruses or Inserting New Genes.

A research team comprised of faculty at Worcester Polytechnic Institute’s (WPI) Life Sciences and Bioengineering Center (LSBC) and investigators at CellThera, a private company also located at the LSBC, has discovered a novel way to turn on stem cell genes in human fibroblasts (skin cells) without the risks associated with inserting extra genes or using viruses.

This discovery opens a new avenue for reprogramming cells that could eventually lead to treatments for a range of human diseases and traumatic injuries by coaxing a patient’s own cells to repair and regenerate the damaged tissues.

The research team reported its findings in the paper “Induction of Stem Cell Gene Expression in Adult Human Fibroblasts without Transgenes,” published online July 21, 2009 (in advance of September print publication) as a “fast track” paper from the journal Cloning and Stem Cells. (Cloning, Stem Cells. 2009 Jul 21.) “We show that by manipulating culture conditions alone, we can achieve changes in fibroblasts that would be beneficial in development of patient-specific cell therapy approaches,” the authors wrote in the paper.

Early on, the emerging field of regenerative medicine focused on embryonic stem cells, which are pluripotent, meaning they can grow into all the tissues of an adult organism. In the pluripotent state, several genes are known to be active, helping to control the stem cells. These genes, including OCT4, SOX2 and NANOG, are accepted as markers of pluripotency because they are active in stem cells, but become dormant once the stem cells begin to differentiate and head down the path to developing into a specific kind of cell type and tissue.

While the study of embryonic stem cells continues to yield important knowledge, research teams around the world are also working to change, or reprogram, fully-differentiated cells like skin cells, back to a more pluripotent state. Called induced pluripotent stem cells (iPS), these reprogrammed cells could be used to regenerate tissue without some of the problems associated with embryonic stem cells, including ethical questions and the potential for embryonic stem cells to be rejected by a patient’s immune system or to grow out of control and cause tumors.

The first induced pluripotent stem cells were created in 2007 by Shinya Yamanaka’s team at Kyoto University in Japan, which inserted extra copies of four known stem cell genes, including OCT4 and SOX2, into human skin cells. Those genes began expressing proteins that changed the skin cells back to a more pluripotent state. This technique, which has since been repeated by other labs and refined to the point were fewer additional genes are needed to achieve reprogramming, was a major scientific breakthrough. Its potential for use in human therapies is limited, however, because inserting new genes into adult cells, either directly or by using viruses to carry the genetic payload, can cause a host of problems.

In the current study, the team at WPI and CellThera turned on the existing, yet dormant, stem cell genes OCT4, SOX2 and NANOG already in the skin cells by lowering the amount of atmospheric oxygen the cells were exposed to, and by adding a protein called fibroblast growth factor 2 (FGF2) to the culture medium. (FGF2 is a naturally occurring protein that is known to be vital for maintaining the pluripotency of embryonic stem cells.)

Furthermore, once the stem cell genes were activated and began expressing proteins, the team found those proteins migrated back into the nucleus of the skin cells, precisely as would occur in induced pluripotent stem cells. “This was an exciting observation,” said Raymond Page, PhD, research assistant professor of biology and biotechnology at WPI and lead author on the paper. “Having these proteins localize to the nucleus is the first step of reprogramming these cells.”

Even more surprising, the team found that the stem cell genes OCT4, SOX2 and NANOG were not completely dormant in untreated skins cells, as was presumed. Those genes were, in fact, sending out messages, but those messages were not being translated into the proteins that do the work of making cells pluripotent. “This was quite unexpected,” said Tanja Dominko, DVM, PhD, associate professor of biology and biotechnology at WPI and president of CellThera. “Not only does this data force us to rethink what the true markers of pluripotency may be, it suggests there is a natural mechanism at work in these cells regulating the stem cell gene expression. That opens a whole new line of inquiry.”

The work in the current study was supported by WPI startup funds and a grant to Dr. Dominko from the National Institutes of Health, and by funding to CellThera from the U.S. Defense Advanced Research Projects Agency (DARPA) and the Army Research Office (ARO).

About CellThera

CellThera is an early-stage biotechnology company focused on inducing somatic cells to revert to multi-potent states to facilitate wound-healing and tissue regeneration. The company was founded by Tanja Dominko, PhD, DVM, now an associate professor of biology and biotechnology at WPI. CellThera is located at WPI’s Life Sciences & Bioengineering Center at Gateway Park in Worcester, Mass.


About Worcester Polytechnic Institute

Founded in 1865 in Worcester, Mass., WPI was one of the nation's first engineering and technology universities. WPI's14 academic departments offer more than 50 undergraduate and graduate degree programs in science, engineering, technology, management, the social sciences, and the humanities and arts, leading to bachelor’s, master’s and PhD degrees. WPI's world-class faculty work with students in a number of cutting-edge research areas, leading to breakthroughs and innovations in such fields as biotechnology, fuel cells, information security, materials processing, and nanotechnology. Students also have the opportunity to make a difference to communities and organizations around the world through the university's innovative Global Perspective Program. There are more than 20 WPI project centers throughout North America and Central America, Africa, Australia, Asia, and Europe.

Contact: Michael Cohen
Media Relations Associate
508-868-4778, mcohen@wpi.edu

Michael Cohen | Worcester Polytechnic Institute
Further information:
http://www.wpi.edu

More articles from Life Sciences:

nachricht Researchers identify potentially druggable mutant p53 proteins that promote cancer growth
09.12.2016 | Cold Spring Harbor Laboratory

nachricht Plant-based substance boosts eyelash growth
09.12.2016 | Fraunhofer-Institut für Angewandte Polymerforschung IAP

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

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

Im Focus: Electron highway inside crystal

Physicists of the University of Würzburg have made an astonishing discovery in a specific type of topological insulators. The effect is due to the structure of the materials used. The researchers have now published their work in the journal Science.

Topological insulators are currently the hot topic in physics according to the newspaper Neue Zürcher Zeitung. Only a few weeks ago, their importance was...

Im Focus: Significantly more productivity in USP lasers

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:...

Im Focus: Shape matters when light meets atom

Mapping the interaction of a single atom with a single photon may inform design of quantum devices

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...

Im Focus: Novel silicon etching technique crafts 3-D gradient refractive index micro-optics

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...

Im Focus: Quantum Particles Form Droplets

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...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

Event News

ICTM Conference 2017: Production technology for turbomachine manufacturing of the future

16.11.2016 | Event News

Innovation Day Laser Technology – Laser Additive Manufacturing

01.11.2016 | Event News

#IC2S2: When Social Science meets Computer Science - GESIS will host the IC2S2 conference 2017

14.10.2016 | Event News

 
Latest News

Researchers identify potentially druggable mutant p53 proteins that promote cancer growth

09.12.2016 | Life Sciences

Scientists produce a new roadmap for guiding development & conservation in the Amazon

09.12.2016 | Ecology, The Environment and Conservation

Satellites, airport visibility readings shed light on troops' exposure to air pollution

09.12.2016 | Health and Medicine

VideoLinks
B2B-VideoLinks
More VideoLinks >>>