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 Ion treatments for cardiac arrhythmia — Non-invasive alternative to catheter-based surgery
20.01.2017 | GSI Helmholtzzentrum für Schwerionenforschung GmbH

nachricht Seeking structure with metagenome sequences
20.01.2017 | DOE/Joint Genome Institute

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

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

Im Focus: Traffic jam in empty space

New success for Konstanz physicists in studying the quantum vacuum

An important step towards a completely new experimental access to quantum physics has been made at University of Konstanz. The team of scientists headed by...

Im Focus: How gut bacteria can make us ill

HZI researchers decipher infection mechanisms of Yersinia and immune responses of the host

Yersiniae cause severe intestinal infections. Studies using Yersinia pseudotuberculosis as a model organism aim to elucidate the infection mechanisms of these...

Im Focus: Interfacial Superconductivity: Magnetic and superconducting order revealed simultaneously

Researchers from the University of Hamburg in Germany, in collaboration with colleagues from the University of Aarhus in Denmark, have synthesized a new superconducting material by growing a few layers of an antiferromagnetic transition-metal chalcogenide on a bismuth-based topological insulator, both being non-superconducting materials.

While superconductivity and magnetism are generally believed to be mutually exclusive, surprisingly, in this new material, superconducting correlations...

Im Focus: Studying fundamental particles in materials

Laser-driving of semimetals allows creating novel quasiparticle states within condensed matter systems and switching between different states on ultrafast time scales

Studying properties of fundamental particles in condensed matter systems is a promising approach to quantum field theory. Quasiparticles offer the opportunity...

Im Focus: Designing Architecture with Solar Building Envelopes

Among the general public, solar thermal energy is currently associated with dark blue, rectangular collectors on building roofs. Technologies are needed for aesthetically high quality architecture which offer the architect more room for manoeuvre when it comes to low- and plus-energy buildings. With the “ArKol” project, researchers at Fraunhofer ISE together with partners are currently developing two façade collectors for solar thermal energy generation, which permit a high degree of design flexibility: a strip collector for opaque façade sections and a solar thermal blind for transparent sections. The current state of the two developments will be presented at the BAU 2017 trade fair.

As part of the “ArKol – development of architecturally highly integrated façade collectors with heat pipes” project, Fraunhofer ISE together with its partners...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

Event News

Sustainable Water use in Agriculture in Eastern Europe and Central Asia

19.01.2017 | Event News

12V, 48V, high-voltage – trends in E/E automotive architecture

10.01.2017 | Event News

2nd Conference on Non-Textual Information on 10 and 11 May 2017 in Hannover

09.01.2017 | Event News

 
Latest News

Helmholtz International Fellow Award for Sarah Amalia Teichmann

20.01.2017 | Awards Funding

An innovative high-performance material: biofibers made from green lacewing silk

20.01.2017 | Materials Sciences

Ion treatments for cardiac arrhythmia — Non-invasive alternative to catheter-based surgery

20.01.2017 | Life Sciences

VideoLinks
B2B-VideoLinks
More VideoLinks >>>