The German Society of Surgery (DGCH) awards the prestigious Von-Langenbeck Prize once a year for the best research work submitted in the field of surgery and related areas. In 2010, the prize was awarded to Dr. Thorsten Walles from the Schillerhöhe Hospital in Stuttgart. In cooperation with his partners, Walles has developed an innovative method for regenerative medicine applications which involves the generation of tissue from the patients’ own cells to replace defective air pipes and oesophagus.
It was a world first in the 56-year history of the prestigious Von-Langenbeck Prize: On 20th April 2010, the prize was awarded for the first time ever to a medical doctor in recognition of the development and successful application of a method used in regenerative medicine. This distinction is a clear sign that this highly innovative cross-sectional field of medicine is gradually moving towards clinical application. Although Walles was individually awarded the prestigious prize, he took care to highlight the cooperative work that led to the development: "At the Fraunhofer IGB, more than 10 years of work have gone into the development, and clinical application was carried out in cooperation with the Schillerhöhe Hospital in Stuttgart," said Walles.
In the lifetime of Bernhard von Langenbeck (1810 to 1887) after whom the prize is named, the treatment concept would have been considered pure science fiction. Even today, after the successful practical application of the method, many would still consider it somewhat futuristic. Although body tissue such as skin or cartilage have been cultivated in the laboratory for therapeutic purposes for quite some time now, the novelty of Walles' method relates to the cultivation of tissue supplied with blood. Vascularisation, i.e. the formation of blood vessels, is a huge obstacle in the field of tissue engineering. The paths leading to the formation of new blood vessels previously seemed to be far too complex for researchers to be able to copy this process in the laboratory.
Air pipes and the oesophagus need to be supplied with blood vessels in order to be able to carry out their proper function. This is why it was not previously possible to treat extensive tumour- or accident-related injuries of these organs. Patients suffered a great deal of pain and could be kept alive only with enormous difficulty. “The common feature of air pipes and the oesophagus is that, in contrast to many other organs, they are not supplied with blood through a few large blood vessels, but through a large number of vessels that are sometimes scarcely bigger than a millimetre in diameter. This makes the transplantation of such organs difficult even though suitable donors would be available,” explains Walles, also highlighting that the pronounced immune function of air pipes and the oesophagus prevents the transplantation of donated organs. “Air pipes and the oesophagus represent important boundaries between the interior of the body and the external environment. They are constantly exposed to bacteria and toxic substances that must be fended off and rendered harmless. The medicinal suppression of the body’s immune defence reactions to prevent the rejection of transplanted organs, makes the transplanted patient highly prone to infections,” said Walles.Artificial prostheses are not a viable alternative either. Supplying artificial implants with blood vessels is problematic, as is the fact that the artificial prosthesis cannot cope with the pathogen load to which it is exposed. “If the prosthesis is not supplied with blood vessels, immune defence cells cannot reach the prosthesis and bacteria tend to attach to the smallest irregularities of the material. Attempts to use glass and silicon as prosthesis materials have also failed to prevent bacteria from settling on the implant,” said Walles who, in cooperation with his wife, Prof. Dr. Heike Walles, and her team at the Fraunhofer IGB in Stuttgart, found a tissue engineering method to circumvent this problem.
The keyword is co-cultivation: the researchers succeeded in cultivating patients' fibroblasts and muscle cells together with microvascular vessels on a biological collagen scaffold. In order to do this, the researchers developed a special bioreactor where artificial tissue is produced under controlled conditions. This tissue is not rejected by the patient who receives the transplant made from his/her own cells and this takes over the defective function of air pipes and the oesophagus. "The tissue is vascularised and prevents bacteria from settling on the implant," said Walles highlighting the advantages of the implant.
The team of researchers and doctors was able to help a patient suffering from advanced lung tumour and the resulting severe respiratory system defects in as much as the patient was able to leave the hospital following the transplantation of laboratory-bred air pipe tissue and lead an independent life until he died from the lung tumour over a year after treatment. Without this regenerative therapy, the patient would have been forced to stay in hospital with an open thorax cavity, be exposed to the constant danger of infection and he would have been unable to speak.
This example shows how regenerative methods are able to give patients a much better quality of life, even in cases when the underlying disease cannot be cured. It is especially true of severe diseases in which patients benefit from tracheal and oesophageal tissue substitutes. "The method is not suitable for all patients, only those who cannot be treated with established methods," said Walles pointing out that around 15 to 20 patients stand to benefit from this type of treatment in Germany every year.
The small number of patients undergoing this innovative treatment only represent the start of future applications. Walles believes that the method also has huge potential in other areas. “The technology can be adapted for applications in other cells and organs. For example, if the researchers manage to seed similar scaffolds with insulin-producing cells and subsequently transplant them, the patient spectrum will expand considerably. Practically all diabetes type I patients stand to benefit from this treatment.” The researchers also plan to use the technology as model system for human tumours and to test anti-tumour substances.This potential very probably played a large part in the selection of the winner of the Von-Langenbeck Prize. “At the award ceremony, our vision of creating a platform technology that has the potential to help many more patients in the future was also highlighted. This type of tissue engineering is still not ready for broad clinical application, but has clearly moved away from the realms of science fiction. In the near future, the method will only be used at specific centres and hospitals,” said Walles. As a chief physician in the Schillerhöhe Hospital, which is part of the Stuttgart-based Robert-Bosch Hospital that specialises in lung diseases, Walles will in future actively contribute to the further development of the method.
PD Dr. Thorsten WallesSchillerhöhe HospitalSolitudestr. 1870839 GerlingenTel.: +49 (0)7156 203-2244E-mail: thorsten.walles(at)klinik-schillerhöhe.de