Atomium Culture

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The Permanent Platform of Atomium Culture brings together some of the most authoritative universities, newspapers and businesses in Europe to increase the movement of knowledge: across borders, across sectors and to the public at large.
La plataforma permanente Atomium Culture reúne a las universidades, periódicos y empresas más prestigiosos de Europa para promover el flujo del conocimiento más allá de fronteras, entre sectores y hacia el público en general.

Healing Chronic Wounds, Trojan Horse–Style

Por: | 08 de mayo de 2014

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By Magdalena Kozakowska, Jagiellonian University in Krakow

Although the term “muscle damage” may sound serious, it is usually a mild injury that nearly all of us experience sometime during our lives. Muscle injuries normally heal quickly and the muscle becomes as efficient as it was before the injury.

Key to the rapid recovery of muscle tissue is a group of small, simple cells known as muscle satellite cells. In undamaged muscle, these cells remain quiescent on the periphery of muscle fibres. But when injury or disease damages muscle tissue, these satellite cells become activated and differentiate to form new muscle fibres that reconstruct the damaged area.

Also essential for quick and effective muscle tissue repair is the formation of new blood vessels around the wound. This process — called angiogenesis — seems to take place much more easily in the presence of muscle satellite cells than in an environment without them.

There are some situations in which damaged muscle does not regenerate quickly; these situations are usually associated with problems of angiogenesis. Without new blood vessel formation, low blood circulation results in nerve and muscle damage, and, eventually, tissue death.

Chronic, non-healing wounds because of poor blood vessel formation are one of the severe complications of diabetes. Wound healing among diabetes patients can be so serious and difficult to treat with standard methods that limb amputation is sometimes required.

As part of our studies in the Department of Medical Biotechnology at Jagiellonian University in Poland, we are asking: if muscle satellite cells are such a wonderful ally in the process of healing muscle tissue, why not to try to use them for other purposes? We are investigating if and how muscle satellite cells could be modified for treating problems caused by blood deficiency, such as wounds in diabetic patients.

We are looking at a protein called heme oxygenese-1, or HO-1. It is a protein that has been shown to have protective properties in other types of tissues, improving new blood vessel formation and decreasing cell mortality. We have worked with muscle satellite cells from mice that we have modified to produce more HO-1. We have found that these modified cells can live better in a high concentration of harmful compounds and also divide more quickly.

Perhaps more importantly, they also produce additional factors that are responsible for satellite cell migration to the area of a wound and are much more viable and active in injured muscle. This suggests that HO-1 could play a beneficial role in diabetes, decreasing the complications of poor blood circulation that results from high blood sugar.

At the present time, we are testing how different HO-1 levels affect the function of muscle satellite cells isolated from mice.

The chief advantage of this approach is the fact that genetic modification is performed outside the organism, the laboratory. That way we can use gene carriers developed from viruses, without the risk of a negative immune response from the organism.

We will then grow satellite cells isolated from the fragments of healthy muscle and genetically modify them in the laboratory to increase the amount of HO-1 they can produce.

We will then place a kind of Trojan horse — our modified satellite cells — in the area of a wound. Our hope is that these modified satellite cells will then become a source of production of the therapeutic protein HO-1. If the results are positive, a similar strategy can then be tested in humans.

Will HO-1 fulfill these expectations? Will satellite cells turn out to be good carriers of genes that can to speed up the process of new blood vessel formation in damaged wound tissue?

Answering those questions will require many more hours of laboratory work. But our work thus far gives us hope.

Magdalena Kozakowska
Jagiellonian University in Krakow
www.atomiumculture.eu

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