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 Nesting aids make agricultural fields attractive for bees
20.07.2017 | Julius-Maximilians-Universität Würzburg

nachricht The Kitchen Sponge – Breeding Ground for Germs
20.07.2017 | Hochschule Furtwangen

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

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

Im Focus: Manipulating Electron Spins Without Loss of Information

Physicists have developed a new technique that uses electrical voltages to control the electron spin on a chip. The newly-developed method provides protection from spin decay, meaning that the contained information can be maintained and transmitted over comparatively large distances, as has been demonstrated by a team from the University of Basel’s Department of Physics and the Swiss Nanoscience Institute. The results have been published in Physical Review X.

For several years, researchers have been trying to use the spin of an electron to store and transmit information. The spin of each electron is always coupled...

Im Focus: The proton precisely weighted

What is the mass of a proton? Scientists from Germany and Japan successfully did an important step towards the most exact knowledge of this fundamental constant. By means of precision measurements on a single proton, they could improve the precision by a factor of three and also correct the existing value.

To determine the mass of a single proton still more accurate – a group of physicists led by Klaus Blaum and Sven Sturm of the Max Planck Institute for Nuclear...

Im Focus: On the way to a biological alternative

A bacterial enzyme enables reactions that open up alternatives to key industrial chemical processes

The research team of Prof. Dr. Oliver Einsle at the University of Freiburg's Institute of Biochemistry has long been exploring the functioning of nitrogenase....

Im Focus: The 1 trillion tonne iceberg

Larsen C Ice Shelf rift finally breaks through

A one trillion tonne iceberg - one of the biggest ever recorded -- has calved away from the Larsen C Ice Shelf in Antarctica, after a rift in the ice,...

Im Focus: Laser-cooled ions contribute to better understanding of friction

Physics supports biology: Researchers from PTB have developed a model system to investigate friction phenomena with atomic precision

Friction: what you want from car brakes, otherwise rather a nuisance. In any case, it is useful to know as precisely as possible how friction phenomena arise –...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

Event News

»We are bringing Additive Manufacturing to SMEs«

19.07.2017 | Event News

The technology with a feel for feelings

12.07.2017 | Event News

Leipzig HTP-Forum discusses "hydrothermal processes" as a key technology for a biobased economy

12.07.2017 | Event News

 
Latest News

Researchers create new technique for manipulating polarization of terahertz radiation

20.07.2017 | Information Technology

High-tech sensing illuminates concrete stress testing

20.07.2017 | Materials Sciences

First direct observation and measurement of ultra-fast moving vortices in superconductors

20.07.2017 | Physics and Astronomy

VideoLinks
B2B-VideoLinks
More VideoLinks >>>