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 Fine organic particles in the atmosphere are more often solid glass beads than liquid oil droplets
21.04.2017 | Max-Planck-Institut für Chemie

nachricht Study overturns seminal research about the developing nervous system
21.04.2017 | University of California - Los Angeles Health Sciences

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

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

Im Focus: Deep inside Galaxy M87

The nearby, giant radio galaxy M87 hosts a supermassive black hole (BH) and is well-known for its bright jet dominating the spectrum over ten orders of magnitude in frequency. Due to its proximity, jet prominence, and the large black hole mass, M87 is the best laboratory for investigating the formation, acceleration, and collimation of relativistic jets. A research team led by Silke Britzen from the Max Planck Institute for Radio Astronomy in Bonn, Germany, has found strong indication for turbulent processes connecting the accretion disk and the jet of that galaxy providing insights into the longstanding problem of the origin of astrophysical jets.

Supermassive black holes form some of the most enigmatic phenomena in astrophysics. Their enormous energy output is supposed to be generated by the...

Im Focus: A Quantum Low Pass for Photons

Physicists in Garching observe novel quantum effect that limits the number of emitted photons.

The probability to find a certain number of photons inside a laser pulse usually corresponds to a classical distribution of independent events, the so-called...

Im Focus: Microprocessors based on a layer of just three atoms

Microprocessors based on atomically thin materials hold the promise of the evolution of traditional processors as well as new applications in the field of flexible electronics. Now, a TU Wien research team led by Thomas Müller has made a breakthrough in this field as part of an ongoing research project.

Two-dimensional materials, or 2D materials for short, are extremely versatile, although – or often more precisely because – they are made up of just one or a...

Im Focus: Quantum-physical Model System

Computer-assisted methods aid Heidelberg physicists in reproducing experiment with ultracold atoms

Two researchers at Heidelberg University have developed a model system that enables a better understanding of the processes in a quantum-physical experiment...

Im Focus: Glacier bacteria’s contribution to carbon cycling

Glaciers might seem rather inhospitable environments. However, they are home to a diverse and vibrant microbial community. It’s becoming increasingly clear that they play a bigger role in the carbon cycle than previously thought.

A new study, now published in the journal Nature Geoscience, shows how microbial communities in melting glaciers contribute to the Earth’s carbon cycle, a...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

Event News

Expert meeting “Health Business Connect” will connect international medical technology companies

20.04.2017 | Event News

Wenn der Computer das Gehirn austrickst

18.04.2017 | Event News

7th International Conference on Crystalline Silicon Photovoltaics in Freiburg on April 3-5, 2017

03.04.2017 | Event News

 
Latest News

New quantum liquid crystals may play role in future of computers

21.04.2017 | Physics and Astronomy

A promising target for kidney fibrosis

21.04.2017 | Health and Medicine

Light rays from a supernova bent by the curvature of space-time around a galaxy

21.04.2017 | Physics and Astronomy

VideoLinks
B2B-VideoLinks
More VideoLinks >>>