Humboldtians in Focus

From Periphery to Cusp

By Anna Frey

For the last 150 years, science has been considering an issue which could save many lives today: is it possible to make a damaged heart regenerate itself? Many researchers have tried in vain to meet this challenge - cell biologist, Felix Engel, has managed: for his achievements in the field of heart cell regeneration he has been granted the Alexander von Humboldt Foundation's Sofja Kovalevskaja Award.

Heart attacks are one of the main causes of death in industrialised countries. In Germany, approximately 280,000 people suffer a heart attack every year; roughly every fourth attack is fatal. A heart attack occurs when a coronary artery becomes narrowed or blocked and the supply of blood to the heart muscle is reduced; this results in the death of cells in the heart muscle which is un able to pump sufficiently to deliver blood to the entire body. Unlike skeletal muscles, the damaged heart of humans or other mammals cannot regenerate itself because the cells are unable to divide. At least, that's what it says in the text books.

Despite this, German cell biologist, Felix Engel, tried to find a way of making adult heart cells divide. After all, he already knew that the injured heart tissue of newts and zebrafish continued regenerating during their entire lifespan. The human heart, on the other hand, only grows by cell division until just after birth - subsequently, heart muscle cells lose the ability to proliferate. Engel admits that what he was trying to do was "not what nature had planned". His critics thought it was simply impossible.

Heart muscle cell of a rat shortly before division: simultaneous administration of a growth factor and inhibition of the protein that usually suppresses division taking effect.
Heart muscle cell of a rat
shortly before division:
simultaneous administration of
a growth factor and inhibition
of the protein that
usually suppresses division
taking effect.
Foto: Georg Scholl

When he was a doctoral student Engel managed to extract the nucleus from the heart muscle cells of rats and to duplicate its genetic material, the DNA. A first, groundbreaking achievement. But in order to continue his investigations aft er completing his doctorate the enthusiastic junior researcher needed a postdoc position, which turned out to be a problem: nearly all the other groups that had worked on the topic gave it up as a bad job. Research applications Engel submitted in the course of his search for funding were turned down with the comment, "Don't reach for the stars." But Engel persisted - and finally found support for his proposal in the figure of Mark Keating, Professor of Cell Biology at Harvard Medical School. "At last I could get going," Engel says gleefully. And he threw himself into his work heart and soul. 

Worldwide stem cell euphoria

He went about trying to make not just the rats' heart cell nucleus divide, as he had for his doctoral thesis, but the intact heart muscle cells, too. To this end, Engel cultivated the cells in a culture medium and stimulated them. "Every single cell contracts and beats like a tiny heart," is the way he describes what happens in the Petri dish. His strategy: he tried to regulate cell division by adding growth factors as these proteins cling to the cell surface and give the cell the signal to divide. If this process could be strategically influenced, the adult heart cells could be induced to divide. Easy, in theory, but in practice it is very difficult to find the right concentration of the right growth factors in order to send the desired signal. So Engel had managed to induce the duplication of the genetic material in the heart cells - but initially the pulsating cells in the dishes failed to divide.

“I wanted to have really water-tight results so that I could take the wind out of the sails of all the sceptics right from the start.”

The shock came in 2001: the renowned scientific journal, Nature, published an article claiming that the heart could be induced to regenerate itself by injecting stem cells, which led to a surge of stem cell euphoria worldwide. "Is that the end?" Engel asked himself, full of doubt. "Who'll be interested in my research now?" Disillusioned, he returned to his lab to finish the experiments he was working on. He was in the process of testing another growth factor called FGF1 when he glanced at a control dish containing an additional factor. "Something in this dish had changed," Engel explains. He looked more closely and couldn't believe his eyes: he had finally found what he had been looking for all this time. The heart cells had divided, and all the genetic material, too. This had been achieved as a result of the interplay between the growth factor FGF1, which induces division, while concurrently inhibiting the protein p38 MAP kinase which normally prevents such division in the heart.

Engel then took his time in publishing his revolutionary discovery. "I wanted to have really water-tight results so that I could take the wind out of the sails of all the sceptics right from the start," he explains. The fact that stem cell therapy didn't fulfil the expectations with regard to cardiac defects aroused in the initial euphoria just put additional wind in the sails of Engel and his discovery. The ambitious cell biologist is obviously proud that he has made his way despite all the opposition. For his discovery he was granted the Alexander von Humboldt Foundation's Sofja Kovalevskaja Award in 2006. Currently valued at 1.2 million EUR, and just increased to a maximum of 1.65 million EUR, it is one of the most attractive awards for junior researchers in Germany. It has allowed Engel to realise one of his great wishes: he has returned to Germany to continue working on his subject with his own research group at the Max Planck Institute for Heart and Lung Research in Bad Nauheim. After all, his findings are supposed to lead to a therapy for people suffering from a heart condition as soon as possible.


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Felix Engel Felix Engel

Dr. Felix Engel, independent research group leader at the Max Planck Institute for Heart and Lung Research in Bad Nauheim, was a postdoctoral researcher at Harvard Medical School (USA). The Sofja Kovalevskaja Award Winner returned to Germany in 2006 to continue his research into heart cell regeneration.

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