Tissue Engineering – The next Step

16. March 2007

Accidents or disease quite often necessitate the replacement of tissue. Tissue engineering raises great hopes here. One project at the University Hospital of Lübeck tests the treatment of diabetic feet with the patient's own cells, their production enabling the growth of new blood vessels. Previous studies confirm this success.

We are getting older every day. Cell by cell dies. Already in 1906, this cognizance won the Nobel prize for the dissector Santiago Ramon y Cajal. To stop the dying of cells – an age old dream of man after all – seems impossible. Then, all of a sudden, a small group of scientists showed up and insisted: No can do, is not true. The genetic engineers and molecular biologists were absolutely sure, that there are methods to slow down the seemingly inexorable decay. Their preferred method, decided the scientists, was to re-grow tissue or even entire organs. Just as there are renewable energies, there should be renewable human body parts. In the back of their heads, they had this vision: Ill organs should not lead to a body system break down any longer. In the future, back-up organs, new vessels, bone- and skin replacements should make the body going again. They should be used whenever pills and such cannot help anymore. So much for visions , but what about reality?

License for cartilage

The chosen way is not unsuccessful. But it takes longer than expected, especially since the methods – like all medical therapies – have to go the proper way through all registration- and admission boards. So the tissue engineers grew tissue from autologous and allogenic cells as well as from stem cells, all to be used for effective treatment of numerous diseases. Cartilage- and bone replacement is possible, but also grown skin replacement to treat patients with burns or badly healing wounds. Many other tissue types and organs are down the experts' “pipeline”.

The Fraunhofer-Institut für Grenzflächen- und Bioverfahrenstechnik IGB in Stuttgart is already certified for production of cartilage replacement. As one of the few non-commercial institutions, the scientists are working on the production of chrondrocytes made from own body material. According to the rules of “Good Manufactering Practice” (GMP) – which is the supreme laboratory standard – they produce cells for further use here. “After a successful breeding, the tissue has to fulfil its specific task” reports Dr. Ulrike Vettel of the research lab. “For example in cartilage cells we prove, whether the cells produce the required collagen type II. If not, the tissue is not cleared for use on the patient.” But this is only the first step: In the future, the scientists hope to produce more cells and tissues such as skin-, bone-, blood- or nerve cells.

Focus on the diabetic foot

Colleagues in Lübeck have committed themselves to another field: The human foot. Not just any foot, but the diabetic one. There is a good reason for that: 10 to 15% of all diabetic patients are confronted at some point of time with the serious issue of the so-called Diabetic Foot Syndrome (DFS). DFS is one of the severe complications of diabetes resulting in about 3,000 cases of amputation in Germany per year. The main reason for the bad healing of the tissue in the lower extremities is a lack of blood circulation in the damaged tissue. Here, in addition to macroangiopathy, mainly the microangiopathy, an affection of the arterioles and capillaries, are responsible for the sick tissue. This does not only cause suffering, but also affects the economy: Annual costs of about 650 million Euros do not make the DFS a cheap disease. Plus – according to the opinion of the WHO – half of the surgeries could be avoided, if there were better therapeutic methods and adequate wound care.

A solution made by the biotech-lab?

Together with the Kompetenzzentrum Tissue Engineering of the Lübeck University (KTE), the Universitätsklinikum Schleswig-Holstein has developed an innovative therapy concept for the diabetic foot syndrome. Further development of this project is supported by the federal state of Schleswig-Holstein, which provides a promotion sum of EUR 825,000 per year for the next three years to the team of Professor Hans-Günther Machens of the KTE.

Own body cells were enriched with growth factors, which is supposed to activate the angiogenesis. Physiological angiogenesis is rather rare in an adult organism, usually during a wound healing process and in the female reproduction organs. In case of a diabetic foot, the angiogenesis does not function normal, thus the wound healing fails. The Lübeck therapy concept targets to change the patient's own cells to make them re-enact the processes of angiogenesis, causing the production of new blood vessels and thus the wound healing.

Just at ‘square one' of the development

During the next three years, the scientists up North will concentrate on the establishment of standardized procedures according to GMP guidelines in order to correspond to the requirements of the regulatory institutions for accreditation. For this purpose, all relevant tests regarding side effect profile and the efficiency within the scope of the project will be made. The scientific head of the research- and development project, Professor Machens, is optimistic: “The success of the project, which we expect based on the studies made so far, will optimize wound healing and give the suffering patients a new perspective of treatment.” In addition, the new technology causes hope to be able to reduce the exorbitant costs for this disease.

This is one of the major reasons why the federal state is so generously supporting the project. Furthermore, the branch of regenerative medicine will be expanded at the university to enable more innovations. The people involved are reflecting also about the possibility of those techniques to provide better help for ischemic damaged tissue of the heart or trouble wounds. In any case, the advantage will be going directly to the patient – on this issue, the hospital directors of the UK-SH Campus Lübeck agree: After a successful laboratory testing, the new cell therapy will be made available to DFS patients as quick as possible.

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