Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

Weizmann Institute Scientists Regenerate Heart Cells in Mice

17.04.2015

When a heart attack strikes, heart muscle cells die and scar tissue forms, paving the way for heart failure. Cardiovascular diseases are a major cause of death worldwide, in part because the cells in our most vital organ do not get renewed.


Weizmann Institute of Science

Two neonatal cardiomyocytes (stained red) undergoing cell division after treatment with NRG1.

As opposed to blood, hair, or skin cells that can renew themselves throughout life, our heart cells cease to divide shortly after birth, with very little renewal in adulthood. New research at the Weizmann Institute of Science provides insight into the question of why the mammalian heart fails to regenerate, and also demonstrated, in adult mice, the possibility of turning back this fate. This research appeared on April 13 in Nature Cell Biology.

Prof. Eldad Tzahor of the Institute’s Department of Biological Regulation thought that part of the answer to the regeneration puzzle might lie in his area of expertise: embryonic development, especially of the heart. Indeed, it was known that a protein called ERBB2 – which is well studied because it can pass along growth signals promoting certain kinds of cancer – plays a role in heart development.

ERBB2 is a specialized receptor – a protein that transmits external messages into the cell. It generally works together with a second, related receptor by binding a growth factor called neuregulin 1 (NRG1) to transmit its message. NGR1 is already being tested in clinical studies as a treatment for heart failure.

Dr. Gabriele D’Uva, a postdoctoral fellow in Prof. Tzahor’s research group, wanted to know exactly how NRG1 and ERBB2 are involved in heart regeneration. In mice, new heart muscle cells can be added for up to a week after birth; in fact, newborn mice can regenerate damaged hearts, while seven-day-old mice cannot.

Dr. D’Uva and research student Alla Aharonov observed that heart muscle cells called cardiomyocytes that were treated with NRG1 continued to proliferate on the day of birth, but that the effect dropped dramatically within a week, even with ample amounts of NRG1. Further investigation showed that the difference between a day and a week was the amount of ERBB2 on the cardiomyocyte membranes.

The team then created mice in which the gene for ERBB2 was “knocked out” in cardiomyocytes. This had a severe impact: the mice had hearts with walls that were thin and balloon-like – a cardiac pathology known as dilated cardiomyopathy. The conclusion was that cardiomyocytes lacking ERBB2 do not divide, even in the presence of NRG1.

Next, the team reactivated the ERBB2 protein in adult mouse heart cells, in which cardiomyocytes normally no longer divide. This resulted in extreme cardiomyocyte proliferation and hypertrophy – excessive growth and development of the individual cardiomyocytes – leading to a giant heart (cardiomegaly) that left little room for blood to enter. Says Prof. Tzahor: “Too little or too much of this protein had a devastating impact on heart function.”

The question then became: if one could activate ERBB2 for just a short period in an adult heart following a heart attack, might it be possible to get the positive results, i.e., cardiac cell renewal, without negative ones such as hypertrophy and scarring?

Testing this idea, the team found that they could, indeed, activate ERBB2 in mice for a short interval only following an induced heart attack, and obtain nearly complete heart regeneration within several weeks. “The results were amazing,” says Prof. Tzahor. “As opposed to extensive scarring in the control hearts, the ERBB2-expressing hearts had completely returned to their previous state.”

Investigation of the regenerative process through live imaging and molecular studies revealed how this happens: the cardiomyocytes “de-differentiate” – that is, they revert to an earlier form, something between an embryonic and an adult cell, which can then divide and differentiate into new heart cells. In other words, the ERBB2 took the cells back a step to an earlier, embryonic form; and then stopping its activity promoted the regeneration process.

In continuing research, Prof. Tzahor and his team began to outline the pathway – the other proteins that respond to the NRG1 message inside the cell. “ERBB2 is clearly at the top of the chain. We have shown that it can induce cardiac regeneration on its own. But understanding the roles of the other proteins in the chain may present us with new drug targets for treating heart disease,” says Dr. D’Uva.

Prof. Tzahor points out that clinical trials of patients receiving the NRG1 treatment might not be overly successful if ERBB2 levels are not boosted as well. He and his team plan to continue researching this signaling pathway to suggest ways of improving the process, which may, in the future, point to ways of renewing heart cells.

Because this pathway is also involved in cancer, well-grounded studies will be needed to understand exactly how to direct the cardiomyocyte renewal signal at the right place, the right time, and in the right amount. “Much more research will be required to see if this principle could be applied to the human heart, but our findings are proof that it may be possible,” he says.

Participating in this research were Profs. Yosef Yarden and Michal Neeman, also of the Department of Biological Regulation. In addition, Prof. Jonathan Leor of Chaim Sheba Medical Center, Israel, and Prof. Richard P. Harvey of the University of South Wales, Australia, contributed to this research.

Prof. Eldad Tzahor’s research is supported by the Louis and Fannie Tolz Collaborative Research Project; the European Research Council; and the estate of Jack Gitlitz.

The Weizmann Institute of Science in Rehovot, Israel, is one of the world’s top-ranking multidisciplinary research institutions. The Institute’s 3,800-strong scientific community engages in research addressing crucial problems in medicine and health, energy, technology, agriculture, and the environment. Outstanding young scientists from around the world pursue advanced degrees at the Weizmann Institute’s Feinberg Graduate School. The discoveries and theories of Weizmann Institute scientists have had a major impact on the wider scientific community, as well as on the quality of life of millions of people worldwide.

Contact Information
Jennifer Manning
Director, Science Content
jennifer@acwis.org
Phone: 212-895-7952

Jennifer Manning | newswise

More articles from Life Sciences:

nachricht New photocatalyst speeds up the conversion of carbon dioxide into chemical resources
29.05.2017 | DGIST (Daegu Gyeongbuk Institute of Science and Technology)

nachricht Copper hydroxide nanoparticles provide protection against toxic oxygen radicals in cigarette smoke
29.05.2017 | Johannes Gutenberg-Universität Mainz

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

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

Im Focus: Strathclyde-led research develops world's highest gain high-power laser amplifier

The world's highest gain high power laser amplifier - by many orders of magnitude - has been developed in research led at the University of Strathclyde.

The researchers demonstrated the feasibility of using plasma to amplify short laser pulses of picojoule-level energy up to 100 millijoules, which is a 'gain'...

Im Focus: Can the immune system be boosted against Staphylococcus aureus by delivery of messenger RNA?

Staphylococcus aureus is a feared pathogen (MRSA, multi-resistant S. aureus) due to frequent resistances against many antibiotics, especially in hospital infections. Researchers at the Paul-Ehrlich-Institut have identified immunological processes that prevent a successful immune response directed against the pathogenic agent. The delivery of bacterial proteins with RNA adjuvant or messenger RNA (mRNA) into immune cells allows the re-direction of the immune response towards an active defense against S. aureus. This could be of significant importance for the development of an effective vaccine. PLOS Pathogens has published these research results online on 25 May 2017.

Staphylococcus aureus (S. aureus) is a bacterium that colonizes by far more than half of the skin and the mucosa of adults, usually without causing infections....

Im Focus: A quantum walk of photons

Physicists from the University of Würzburg are capable of generating identical looking single light particles at the push of a button. Two new studies now demonstrate the potential this method holds.

The quantum computer has fuelled the imagination of scientists for decades: It is based on fundamentally different phenomena than a conventional computer....

Im Focus: Turmoil in sluggish electrons’ existence

An international team of physicists has monitored the scattering behaviour of electrons in a non-conducting material in real-time. Their insights could be beneficial for radiotherapy.

We can refer to electrons in non-conducting materials as ‘sluggish’. Typically, they remain fixed in a location, deep inside an atomic composite. It is hence...

Im Focus: Wafer-thin Magnetic Materials Developed for Future Quantum Technologies

Two-dimensional magnetic structures are regarded as a promising material for new types of data storage, since the magnetic properties of individual molecular building blocks can be investigated and modified. For the first time, researchers have now produced a wafer-thin ferrimagnet, in which molecules with different magnetic centers arrange themselves on a gold surface to form a checkerboard pattern. Scientists at the Swiss Nanoscience Institute at the University of Basel and the Paul Scherrer Institute published their findings in the journal Nature Communications.

Ferrimagnets are composed of two centers which are magnetized at different strengths and point in opposing directions. Two-dimensional, quasi-flat ferrimagnets...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

Event News

Marine Conservation: IASS Contributes to UN Ocean Conference in New York on 5-9 June

24.05.2017 | Event News

AWK Aachen Machine Tool Colloquium 2017: Internet of Production for Agile Enterprises

23.05.2017 | Event News

Dortmund MST Conference presents Individualized Healthcare Solutions with micro and nanotechnology

22.05.2017 | Event News

 
Latest News

New insights into the ancestors of all complex life

29.05.2017 | Earth Sciences

New photocatalyst speeds up the conversion of carbon dioxide into chemical resources

29.05.2017 | Life Sciences

NASA's SDO sees partial eclipse in space

29.05.2017 | Physics and Astronomy

VideoLinks
B2B-VideoLinks
More VideoLinks >>>