Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

Research Scientists Home In on Chemicals Needed to Reprogram Cells

06.12.2010
For Immediate Release – Scripps Research Institute scientists have made a significant leap forward in the drive to find a way to safely reprogram mature human cells and turn them into stem cells, which can then change into other cell types, such as nerve, heart, and liver cells. The ability to transform fully mature adult cells such as skin cells into stem cells has potentially profound implications for treating many diseases.

In research published in the December 3, 2010 issue of Cell Stem Cell, Scripps Research Associate Professor Sheng Ding, PhD, reports a novel cocktail of drug-like small molecules that, with the assistance of a gene called Oct4, enables reprogramming of human skin cells into stem cells.

“Our ultimate goal is to generate induced pluripotent stem cells with defined small molecules,” Ding said. “This would offer a fundamentally new method and significant advantages over previous methods, such as genetic manipulation or more difficult-to-manufacture biologics.”

Using small-molecule compounds to reprogram adult human cells back to their pluripotent state — able to change into all other cell types — avoids the ethical controversy around embryonic stem cell research, and paves the way for the large-scale production of stem cells that could be used inexpensively and consistently in drug development. Cures for Alzheimer’s, Parkinson’s, and many other diseases might be possible if new cells could be created from a patient’s own cells to replace those that have succumbed to disease or injury.

Substituting Chemicals for Genes

Scientists discovered in 2007 that fully differentiated mature cells, such as skin cells, could be “reprogrammed” to become pluripotent by using four transcription genes. One problem with this technique is that these genes, once inserted into a cell, permanently alter the host cell’s DNA.

“There are many concerns when the host cell’s genome is manipulated,” Ding says. “One major worry is that since the four genes are [cancer-causing] oncogenes, they could induce tumors or interrupt functions of other normal genes.”

Because of this danger, scientists have been searching for methods that could induce reprogramming without the use of these cancer-causing genes. The method the Ding lab has been pioneering — using small, synthetic molecules — represents a fundamentally different approach from the previous methods.

“We are working toward creating drugs that are totally chemically defined, where we know every single component and precisely what it does, without causing genetic damage,” Ding says.

Breaking New Ground

Scientists have known for at least 50 years that a cell’s identity is reversible if given the right signal — cells go forward to become mature, functional cells or they can go backward to become primitive cells. In order for cellular reprogramming to be safe and practical enough to use in cell therapy, researchers have sought an efficient, reliable way to trigger the reprogramming process.

In 2008, the Ding lab reported finding small molecules that could replace two of the required four genes. Now, two years later, through extraordinary effort and unique screening strategy, the lab made a major leap forward by finding a way to replace three out of the four genes.

“We are only one step away from the ultimate goal, which would represent a revolutionary technology,” Ding says.

The new study also revealed that the novel compound facilitates a novel mechanism in reprogramming: the metabolic switch from mitochondrial respiration to glycolysis, an important mechanism for tissue regeneration. The small molecules Ding and his colleagues found promote reprogramming by facilitating such metabolic switching — an entirely new understanding of reprogramming.

A future goal is to replace Oct4, a master regulator of pluripotency, in the chemical cocktail. “ That would be the last step toward achieving the Holy Grail,” Ding says. “Our latest discovery brings us one step closer to this dream.”

The first author of the paper, “Reprogramming of Human Primary Somatic Cells by OCT4 and Chemical Compounds,” is Saiyong Zhu of The Scripps Research Institute. In addition to Ding and Zhu, other authors include Wenlin Li, Hongyan Zhou, Wanguo Wei, Rajesh Ambasudhan, Tongxiang Lin, and Janghwan Kim, also of Scripps Research, and Kang Zhang of the Department of Ophthalmology and Shiley Eye Center, and Institute for Genomic Medicine, University of California, San Diego, La Jolla. See http://www.cell.com/cell-stem-cell/fulltext/S1934-5909%2810%2900637-5

Sheng Ding is supported by funding from Fate Therapeutics, California Institute for Regenerative Medicine, the National Institutes of Health (NICHD, NHLBI, and NIMH), Prostate Cancer Foundation, Esther B. O’Keeffe Foundation, and The Scripps Research Institute. Kang Zhang is supported by grants from National Eye Institute/National Institute of Health, VA Merit Award, the Macula Vision Research Foundation, Research to Prevent Blindness, Burroughs Wellcome Fund Clinical Scientist Award in Translational Research, and Dick and Carol Hertzberg Fund.

About The Scripps Research Institute

The Scripps Research Institute is one of the world's largest independent, non-profit biomedical research organizations, at the forefront of basic biomedical science that seeks to comprehend the most fundamental processes of life. Scripps Research is internationally recognized for its discoveries in immunology, molecular and cellular biology, chemistry, neurosciences, autoimmune, cardiovascular, and infectious diseases, and synthetic vaccine development. An institution that evolved from the Scripps Metabolic Clinic founded by philanthropist Ellen Browning Scripps in 1924, Scripps Research currently employs approximately 3,000 scientists, postdoctoral fellows, scientific and other technicians, doctoral degree graduate students, and administrative and technical support personnel. Headquartered in La Jolla, California, the institute also includes Scripps Florida, whose researchers focus on basic biomedical science, drug discovery, and technology development. Scripps Florida is located in Jupiter, Florida. For more information, see www.scripps.edu.

Mika Ono | Newswise Science News
Further information:
http://www.scripps.edu

More articles from Life Sciences:

nachricht Individual Receptors Caught at Work
19.10.2017 | Julius-Maximilians-Universität Würzburg

nachricht Rapid environmental change makes species more vulnerable to extinction
19.10.2017 | Universität Zürich

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

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

Im Focus: Neutron star merger directly observed for the first time

University of Maryland researchers contribute to historic detection of gravitational waves and light created by event

On August 17, 2017, at 12:41:04 UTC, scientists made the first direct observation of a merger between two neutron stars--the dense, collapsed cores that remain...

Im Focus: Breaking: the first light from two neutron stars merging

Seven new papers describe the first-ever detection of light from a gravitational wave source. The event, caused by two neutron stars colliding and merging together, was dubbed GW170817 because it sent ripples through space-time that reached Earth on 2017 August 17. Around the world, hundreds of excited astronomers mobilized quickly and were able to observe the event using numerous telescopes, providing a wealth of new data.

Previous detections of gravitational waves have all involved the merger of two black holes, a feat that won the 2017 Nobel Prize in Physics earlier this month....

Im Focus: Smart sensors for efficient processes

Material defects in end products can quickly result in failures in many areas of industry, and have a massive impact on the safe use of their products. This is why, in the field of quality assurance, intelligent, nondestructive sensor systems play a key role. They allow testing components and parts in a rapid and cost-efficient manner without destroying the actual product or changing its surface. Experts from the Fraunhofer IZFP in Saarbrücken will be presenting two exhibits at the Blechexpo in Stuttgart from 7–10 November 2017 that allow fast, reliable, and automated characterization of materials and detection of defects (Hall 5, Booth 5306).

When quality testing uses time-consuming destructive test methods, it can result in enormous costs due to damaging or destroying the products. And given that...

Im Focus: Cold molecules on collision course

Using a new cooling technique MPQ scientists succeed at observing collisions in a dense beam of cold and slow dipolar molecules.

How do chemical reactions proceed at extremely low temperatures? The answer requires the investigation of molecular samples that are cold, dense, and slow at...

Im Focus: Shrinking the proton again!

Scientists from the Max Planck Institute of Quantum Optics, using high precision laser spectroscopy of atomic hydrogen, confirm the surprisingly small value of the proton radius determined from muonic hydrogen.

It was one of the breakthroughs of the year 2010: Laser spectroscopy of muonic hydrogen resulted in a value for the proton charge radius that was significantly...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

Event News

ASEAN Member States discuss the future role of renewable energy

17.10.2017 | Event News

World Health Summit 2017: International experts set the course for the future of Global Health

10.10.2017 | Event News

Climate Engineering Conference 2017 Opens in Berlin

10.10.2017 | Event News

 
Latest News

Electrode materials from the microwave oven

19.10.2017 | Materials Sciences

New material for digital memories of the future

19.10.2017 | Materials Sciences

Physics boosts artificial intelligence methods

19.10.2017 | Physics and Astronomy

VideoLinks
B2B-VideoLinks
More VideoLinks >>>