A research project at the University for Continuing Education Krems, funded as part of the Lower Austria Technopol Program, is developing a blood vessel chamber for cultivating human umbilical cord vessels under near-physiological conditions. The aim is to preserve and regenerate the glycocalyx, a key structure of the endothelium – the thin cellular lining of blood vessels – that plays a central role in vascular function. The resulting animal-free test system will significantly advance cardiovascular research by providing new insights into the mechanisms underlying thrombosis and sepsis.
Cardiovascular diseases are among the most common causes of death worldwide and are often associated with changes in vascular tissue. The exact mechanisms of such diseases, which are caused by thrombosis or sepsis, are still largely unexplored. When they are studied, it is often in animal experiments or in vitro models. However, the latter cannot replicate the in vivo situation, which leads to animal experiments that cannot fully reflect the physiological conditions in humans.
Cultivation of human umbilical cords
"The research project is based on the hypothesis that a human umbilical cord, which has two arteries and one vein, can be cultivated in a ‘blood vessel chamber’ developed in-house. The aim is to preserve or regenerate the glycocalyx, a carbohydrate-rich layer on the endothelial surface. This would provide a native human blood vessel for research purposes," says Christoph Bauer, project leader at the Center for Regenerative Medicine at the University for Continuing Education Krems. The project has four objectives: firstly, to produce a special chamber for the cultivation of a human umbilical cord; second, the establishment of optimal cultivation conditions for an intact glycocalyx and upright cell metabolism; third, the further development of analytical methods for characterizing the glycocalyx and endothelial cells; and fourth, the establishment of two models to replace or reduce animal testing in thrombosis and sepsis research.
The research project is based on the hypothesis that a human umbilical cord (image), which has two arteries and one vein, can be cultivated in a self-developed ‘blood vessel chamber’. The aim is to preserve or regenerate the glycocalyx, a carbohydrate-rich layer on the endothelial surface. This would provide a native human blood vessel for research purposes.
A look inside the “living” vessel
The blood vessels of the umbilical cord are connected to the culture chamber and continuously incubated with an endothelial nutrient medium in flow. Regularly collected tissue samples are used to examine the intact glycocalyx and metabolically active endothelial cells. Flow cytometry and multiplex assays monitor the influence of adapted in vivo culture conditions (e.g., human serum, blood cells). Once the blood vessel chamber has been established, a near-native test system for cardiovascular diseases will be available, which can be analyzed using biochemical (multiplex assay, ELISA), molecular biological (qPCR), and microscopic (SEM, histology, confocal microscopy) methods. Using the above-mentioned techniques, a glycocalyx regeneration model will be established that can be used for the development of other models. In a further step, sepsis, which is often triggered by bacterial germs, will be induced in a model by adding lipopolysaccharide. This leads to a breakdown of the glycocalyx through inflammatory mechanisms. The degradation can be detected by proteins (e.g., syndecan-1) or enzymes (metalloproteinases, heparinas) in the supernatant and made visible by electron microscopy (SEM).
Animal-free research into blood vessel diseases
The newly developed “blood vessel chamber” is intended to be a first step toward animal-free research into blood vessel diseases and their consequences, with the aim of completely replacing animal testing in this area in the future.
The synergistic scientific and technical support provided by the corresponding interdisciplinary team led by Associate Professor Jens Hartmann and Professor Stefan Nehrer at the University for Continuing Education is expected to contribute to the successful implementation of the planned project.
Project info:
Title: Development of a new human-based ex vivo blood vessel model – glycocalyx
Duration: 2025-2027
Funding body: Technopol Program Lower Austria/ERDF (Project number: WST3-F-5030664/039-2024)
Project manager: Dipl.-Ing. Christoph Bauer, PhD BSc BA, Center for Regenerative Medicine at the University for Continuing Education Krems
Tags
