Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

Ordinary heart cells become 'biological pacemakers' with injection of a single gene

17.12.2012
Cedars-Sinai Heart Institute researchers have reprogrammed ordinary heart cells to become exact replicas of highly specialized pacemaker cells by injecting a single gene (Tbx18)–a major step forward in the decade-long search for a biological therapy to correct erratic and failing heartbeats.

The advance will be published in the Jan 8 issue of Nature Biotechnology and also will be available today on the journal's website.

"Although we and others have created primitive biological pacemakers before, this study is the first to show that a single gene can direct the conversion of heart muscle cells to genuine pacemaker cells. The new cells generated electrical impulses spontaneously and were indistinguishable from native pacemaker cells," said Hee Cheol Cho, PhD., a Heart Institute research scientist.

Pacemaker cells generate electrical activity that spreads to other heart cells in an orderly pattern to create rhythmic muscle contractions. If these cells go awry, the heart pumps erratically at best; patients healthy enough to undergo surgery often look to an electronic pacemaker as the only option for survival.

The heartbeat originates in the sinoatrial node (SAN) of the heart's right upper chamber, where pacemaker cells are clustered. Of the heart's 10 billion cells, fewer than 10,000 are pacemaker cells, often referred to as SAN cells. Once reprogrammed by the Tbx18 gene, the newly created pacemaker cells – "induced SAN cells" or iSAN cells – had all key features of native pacemakers and maintained their SAN-like characteristics even after the effects of the Tbx18 gene had faded.

But the Cedars-Sinai researchers, employing a virus engineered to carry a single gene (Tbx18) that plays a key role in embryonic pacemaker cell development, directly reprogrammed heart muscle cells (cardiomyocytes) to specialized pacemaker cells. The new cells took on the distinctive features and function of native pacemaker cells, both in lab cell reprogramming and in guinea pig studies.

Previous efforts to generate new pacemaker cells resulted in heart muscle cells that could beat on their own. Still, the modified cells were closer to ordinary muscle cells than to pacemaker cells. Other approaches employed embryonic stem cells to derive pacemaker cells. But, the risk of contaminating cancerous cells is a persistent hurdle to realizing a therapeutic potential with the embryonic stem cell-based approach. The new work, with astonishing simplicity, creates pacemaker cells that closely resemble the native ones free from the risk of cancer.

For his work on biological pacemaker technology, Cho, the article's last author, recently won the Louis N. and Arnold M. Katz Basic Research Prize, a prestigious young investigator award of the American Heart Association.

"This is the culmination of 10 years of work in our laboratory to build a biological pacemaker as an alternative to electronic pacing devices," said Eduardo Marbán, MD, PhD, director of the Cedars-Sinai Heart Institute and Mark S. Siegel Family Professor, a pioneer in cardiac stem cell research. A clinical trial of Marbán's stem cell therapy for heart attack patients recently found the experimental treatment helped damaged hearts regrow healthy muscle.

If subsequent research confirms and supports findings of the pacemaker cell studies, the researchers said they believe therapy might be administered by injecting Tbx18 into a patient's heart or by creating pacemaker cells in the laboratory and transplanting them into the heart. But additional studies of safety and effectiveness must be conducted before human clinical trials could begin.

The study was supported by the Cedars-Sinai Board of Governors Heart Stem Cell Center, the Heart Rhythm Society, the Heart and Stroke Foundation of Canada, the American Heart Association (12SDG9020030), the National Heart, Lung, and Blood Institute (1R01HL111646-01A1), and the Mark S. Siegel Family Professorship. The authors report that they have no conflicts of interest.

Citation: Nature Biotechnology, "Transcription factor-driven conversion of quiescent cardiomyocytes to pacemaker cells," online Dec. 16, 2012; print publication in issue dated Jan. 8, 2013.

Embargoed until 10 am PST (1 pm EST; 6 pm London UK), Sunday, Dec. 16, 2012

VIDEOLINK ENABLED
Thanks to a new, state-of-the-art in-house studio, Cedars-Sinai Medical Center can now instantly broadcast quality HD video directly to newsrooms around the world.

Sally Stewart | EurekAlert!
Further information:
http://www.cshs.org

More articles from Life Sciences:

nachricht Single-stranded DNA and RNA origami go live
15.12.2017 | Wyss Institute for Biologically Inspired Engineering at Harvard

nachricht New antbird species discovered in Peru by LSU ornithologists
15.12.2017 | Louisiana State University

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

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

Im Focus: Error-free into the Quantum Computer Age

A study carried out by an international team of researchers and published in the journal Physical Review X shows that ion-trap technologies available today are suitable for building large-scale quantum computers. The scientists introduce trapped-ion quantum error correction protocols that detect and correct processing errors.

In order to reach their full potential, today’s quantum computer prototypes have to meet specific criteria: First, they have to be made bigger, which means...

Im Focus: Search for planets with Carmenes successful

German and Spanish researchers plan, build and use modern spectrograph

Since 2016, German and Spanish researchers, among them scientists from the University of Göttingen, have been hunting for exoplanets with the “Carmenes”...

Im Focus: First-of-its-kind chemical oscillator offers new level of molecular control

DNA molecules that follow specific instructions could offer more precise molecular control of synthetic chemical systems, a discovery that opens the door for engineers to create molecular machines with new and complex behaviors.

Researchers have created chemical amplifiers and a chemical oscillator using a systematic method that has the potential to embed sophisticated circuit...

Im Focus: Long-lived storage of a photonic qubit for worldwide teleportation

MPQ scientists achieve long storage times for photonic quantum bits which break the lower bound for direct teleportation in a global quantum network.

Concerning the development of quantum memories for the realization of global quantum networks, scientists of the Quantum Dynamics Division led by Professor...

Im Focus: Electromagnetic water cloak eliminates drag and wake

Detailed calculations show water cloaks are feasible with today's technology

Researchers have developed a water cloaking concept based on electromagnetic forces that could eliminate an object's wake, greatly reducing its drag while...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

Event News

See, understand and experience the work of the future

11.12.2017 | Event News

Innovative strategies to tackle parasitic worms

08.12.2017 | Event News

AKL’18: The opportunities and challenges of digitalization in the laser industry

07.12.2017 | Event News

 
Latest News

Error-free into the Quantum Computer Age

18.12.2017 | Physics and Astronomy

Disarray in the brain

18.12.2017 | Studies and Analyses

2 million euros in funding for new MR-compatible electrophysiological brain implants

18.12.2017 | Medical Engineering

VideoLinks
B2B-VideoLinks
More VideoLinks >>>