Hope for patients with vascular occlusion

IVB IN VITRO BIOTEC begins producing coated vascular prostheses

Stuttgart-based biotechnology company IVB IN VITRO BIOTEC GmbH has begun producing cell-coated vascular prostheses. The prostheses are coated with the patient's own endothelial cells (vascular wall cells) to prevent activation of the body's coagulation system, which would lead to reocclusion of the vascular segment. The company produces the world-first prostheses in its own clean-room lab for Berlin-based VasoTissue Technologies GmbH.

Heart attacks are the biggest killer in the industrialised world. It is caused by severe narrowing of the coronary vessels, known as arteriosclerosis or hardening of the arteries. Bypass operations have proven over many years to be an effective treatment method and involve removing veins or arteries from another part of the patient's body and using these to make a detour round the blocked part of the coronary artery. However, this procedure is not possible on certain patients and vascular prostheses are a viable alternative in such cases. Nonetheless, the body's coagulation system interprets these plastic tubes as foreign bodies or a defect in the vascular wall, leading to blood clotting and ultimately the possibility of reocclusion. For almost two decades, experts have been trying in vain to solve this problem by lining the inner plastic surface with the patient's own endothelial cells with the aim of "concealing" the surface of the prosthesis from the coagulation system. It proved impossible to give the prosthesis a lasting coating as the flow of blood repeatedly washed away the vascular wall coating.

VasoTissue Technologies GmbH has now developed a unique method that prevents this from happening by "training" the cells coating the prosthesis. Scientists from IVB IN VITRO BIOTEC GmbH isolate the patient's endothelial cells from a piece of his vein. The cells are initially cultivated and transferred to the vascular prosthesis through uniform sedimentation. Biotechnological methods are used to train the cells. The prosthesis is then inserted in an artificial cardiovascular system and the flow of fluid is systematically increased. The cells increasingly develop adhesion molecules, ensuring strong attachment to the prosthesis. By coating the prosthesis with the body's own cells, an intact vascular wall is presented to the coagulation system, thereby reducing the risk of reocclusion of the vessel.

The customer for this world-first technique is VasoTissue Technologies GmbH. The Berlin-based company has developed vascular prostheses that are already internationally patent-protected. However, the company requires a production partner that not only has experience in cell cultures, tissue engineering, molecular biology and analytics, but also has the necessary approved laboratory space. The coated prostheses are categorised as pharmaceuticals, and strict guidelines and conditions govern their production. The production process has to comply exactly with German pharmaceuticals and pharmacological legislation and GMP guidelines. Transport of the finished product from the clean-room lab to the operating table alone shows the complexity involved in correct handling of the material. The prosthesis is given three layers of packaging in the lab and delivered to the hospital door by courier in this packaging. The sterile secondary packaging may be opened at the operating table. However, only the surgeon can remove the primary packaging, which has to be completely sterile.

To guarantee absolute sterility, IVB IN VITRO BIOTEC GmbH requires a high-tech clean room that is not only sterile, but also free of any particles. This is achieved using high-tech air-conditioning technology with special filters and 40 air changes per minute. Chief Operating Officer Dr. Marion Mappes says of the GMP (Good Manufacturing Practice) lab, "The staff all wear special clean-room clothing that even covers their face as the eyebrows and skin give off particles that must not be present."

The fact the IVB obtained the clean-room premises and production licence so quickly is due to the excellent network in the STERN region. Joachim Wilke from i.con innovation GmbH recognised the opportunities offered by cooperation between the two biotech companies VasoTissue Technologies GmbH and IVB IN VITRO BIOTEC GmbH. Wilke, CEO of the Stuttgart-based consulting company that specialises in supporting young technology companies from the life sciences sector in the early stages of their corporate development and in securing venture capital funding, brought the two companies together. Buck-Chemie GmbH, a shareholder in IVB IN VITRO BIOTEC GmbH, was immediately convinced of the partnership's potential and invested in developing the GMP lab.

The body responsible for pharmaceutical safety within the Tübingen regional government office (Regierungspräsidium Tübingen) was also impressed by the premises and the specialist technical facilities at IVB IN VITRO BIOTEC GmbH and offered its full cooperation. "We examined everything necessary to meet the requirements," says Dr. Mappes. "The regional government office gave us the manufacturing licence after just a short time. They recognised that a young company cannot wait months to receive authorisation. IVB's accreditation as a testing laboratory and the existing approvals from the Tübingen and Stuttgart regional government offices relating to genetic engineering, infection prevention and animal disease prevention were extremely helpful in the approval process. However, it was the quality management procedures in place at IVB IN VITRO BIOTEC GmbH that ultimately convinced the responsible authorities." BioRegio STERN Managing Director Dr. Klaus Eichenberg is well acquainted with the challenges that face young biotech companies. As early as 2004, he commissioned a study into the "economic development and the future of regenerative medicine in Germany". "The more concerted the effort made to promote open communication, the faster regenerative medicine will gain in economic significance. Despite the comparably unfavourable conditions, Germany occupies a leading position worldwide when it comes to tissue engineering," he says.

IVB's Chief Operating Officer Dr. Mappes is convinced of the company's success. "The demand is there. As word gets round about what we are doing, it will well and truly open the floodgates. We hope that demand will grow steadily, not just in Germany, but across Europe," she says. The fact that the company will have to expand its existing 13-strong workforce goes without saying. "As soon as the project is running smoothly and we receive more orders, we'll look to employing more staff." The strict GMP requirements play an important role in this recruitment: "When a patient's prosthesis leaves the lab, the clean-room workstation has to be completely decontaminated. The staff in the lab also have to be changed and a second team begins working on a new patient's cells."

The IVB team hopes to remove cell material from the first patient at the end of June and the coated prosthesis will be fitted three weeks later. Dr. Manrico Paulitschke knows what this means for the patient. "At this stage of proving effectiveness, only patients for whom traditional methods no longer work will be treated with this technique, i.e. patients whose arteries or veins can no longer be removed," says Dr. Paulitschke, CEO of VasoTissue Technologies. "This is the only solution for these patients." The technique is new, but the risk is slight. "The only danger is that the cells come away from the wall of the prosthesis," explains Dr. Paulitschke. The effectiveness of the technique can be considered proven when ten patients have been successfully treated and the team expects the initial results in around six months. No health insurance companies currently reimburse the costs of the treatment, but Dr. Paulitschke is optimistic about the future. "Once the initial patients have been successfully treated, we will be well on the way to gaining approval from the health insurers."