BMBF funds MHH project on heart support system with three million euros
Status: 21. July 2021
More than 9,000 people in Germany are on the waiting list for a donor organ, about 700 of them are waiting for a heart. Donor organs are in short supply, artificially produced replacement organs are still dreams of the future. But medicine is getting closer to this goal - also at the MHH. In the research project "3D-Heart-2B", scientists from the Clinic for Cardiac, Thoracic, Transplantation and Vascular Surgery (HTTG) and the Leibniz Research Laboratories for Biotechnology and Artificial Organs (LEBAO) want to develop a biological heart support system. So-called induced pluripotent stem cells (iPS cells) from genetically reprogrammed human tissue cells are used to produce heart muscle cells and blood vessel-lining endothelial cells. These are to form the basic building block for a tubular heart prosthesis. In 2020, the project emerged as the winner of the nationwide competition "Organ Replacement from the Laboratory" of the Federal Ministry of Education and Research (BMBF) and was launched at the end of January. The BMBF is supporting the development of the single-chamber heart with three million euros for three years.
Such an implant could, for example, help patients with congenital heart defects in whom only one chamber of the heart works for hereditary reasons. A healthy heart has two chambers that are separated from each other by the cardiac septum. The left ventricle pumps oxygen-rich blood into the aorta, the right ventricle pumps oxygen-poor blood into the lungs. If only one ventricle is present or functional from birth, it supplies both the body and lung arteries. "These patients have mixed blood in the heart and have to undergo a so-called Fontan operation in childhood, in which the circuits are separated," explains HTTG Clinic Director Professor Dr Axel Haverich. However, the incomplete heart still has a reduced pumping capacity.
A healthy heart has two chambers that are separated from each other by the cardiac septum. The left ventricle pumps oxygen-rich blood into the aorta, the right ventricle pumps oxygen-poor blood into the lungs. If only one ventricle is present or functional from birth, it supplies both the body and lung arteries. "These patients have mixed blood in the heart and have to undergo a so-called Fontan operation in childhood, in which the circuits are separated," explains HTTG Clinic Director Professor Dr Axel Haverich. However, the incomplete heart still has a reduced pumping capacity.
Development according to the modular principle
The biological heart prosthesis made from fibrin, heart muscle cells and heart valves is intended to compensate for this shortcoming in the future. The project is coordinated by Professor Dr. Ina Gruh, who is pleased that "this project precisely reflects our profile and our experience from 20 years of organ replacement and stem cell research at the MHH". The single-chamber heart is to be created in a modular fashion. The scientists want to develop biological components piece by piece and assemble them according to the modular principle. First, still undifferentiated, so-called pluripotent iPS cells will be produced and then specifically converted into heart muscle cells and vascular cells by molecular biological signals. "For later clinical application, we produce the iPS cells from the patients' own body cells," explains Professor Dr Ulrich Martin, scientific director of LEBAO. Together with the protein fibrin as a support scaffold, a heart muscle tube is produced from them. Fibrin is the main component of blood clotting and is accepted by the immune system as a biological matrix. The tube is then equipped with vessels, clamped in special bioreactors and perfused.
Heart valves direct the blood flow
"We have already successfully developed such heart muscle tubes," says Professor Gruh. In a further step, the tube will be lined on the inside with endothelial cells and equipped with two heart valves. "We use so-called decellularised homografts for this," explains the biochemist. They come from the usually well-preserved heart valves of otherwise damaged hearts, which are exchanged for a healthy organ during a transplant. Purified from the body's own cells, the homografts serve as an immune-neutral basic scaffold for new heart valves. Through the heart valves, the blood flow can be directed in one direction, just like in a real half of the heart. In order to finally create a compact heart tube, several tubes equipped with vessels are to be inserted into each other and thus increase the strength of the ventricular wall.
However, the specially developed larger device for fibrin compression constructed at the MHH research workshops is still missing for this. "But we have already tried out many things in preliminary work and seen that it works," says Professor Gruh. However, there is still a lot of work ahead of the research team before the single-chamber heart can be used. First, the required tissues would have to be reliably produced. "At the end of the project period, however, we definitely want to be ready to test the construct in an animal model," the scientist emphasises. Later clinical studies will then show whether the heart prosthesis from the MHH also works in humans.
Who does what?
For the 3D Heart 2B project, an interdisciplinary team from the fields of biology, biochemistry and medicine at the HTTG clinic and the MHH research facility LEBAO are working together in a competence network.
Dr Robert Zweigerdt and Dr Ruth Olmer produce cardiac muscle cells and endothelial cells from induced pluripotent stem cells.
Dr Thomas Aper is a vascular surgeon and an expert in the fibrin prosthesis he developed.
Professor Dr. Ina Gruh grows tubes from heart muscle cells and the carrier protein fibrin; she also checks the function of the heart prosthesis.
Dr Andres Hilfiker is responsible for the vascularisation of the heart prosthesis in specially made bioreactors.
Professor Dr Andreas Martens examines how the single-chamber heart works in an animal model.
Author: Kirsten Pötzke