BREATH scientist develops protocol for the generation of clinically relevant amounts of endothelial cells

Endothelial cells (ECs) are involved in a variety of cellular processes, e.g. the immune response, inflammation and regulation of blood flow. They are used in cell therapies and are an important component in the production of tissue constructs as well as in in vitro disease models. Although the isolation of primary ECs from different sources has been shown, the generation of sufficient cell levels in stable quality still remains a challenge. Ruth Olmer has now developed a scalable protocol for the generation of ECs from human induced pluripotent stem cells.

Endothelial cells (ECs) - specialized, flat cells that line the inside of the blood vessels, are involved in various cellular responses. Changes in cellular function are associated with a number of pathological processes such as arteriosclerosis, pumping failure of the heart (congestive heart failure) or pulmonary hypertension (pulmonary hypertension). Therefore, ECs have been used for some time as in vitro models to study, for example, vascular dysfunctions. In addition, ECs are used as important components in so-called tissue engineering. Producing sufficient quantities of consistently high quality ECs for clinical applications, e.g. cell therapy, however, still remain a major challenge. An alternative cell source to the limited primary ECs are human induced pluripotent stem cells (hiPSC). These cells are produced by the so-called reprogramming of body cells and are not only able to multiply infinitely, but can also differentiate into all cells of the body, including ECs. In addition, the reprogramming allows the production of patient - or disease-specific cells.

In lung research, one desired application of ECs is, Extracorporeal Membrane Oxygenation, (ECMO). In this organ replacement procedure, a machine temporarily takes over the respiratory functions of a patient. Here, blood is pumped continuously through a so-called oxygenator, which uses membranes to replace the gas exchange in the lungs: carbon dioxide is removed and the blood is oxygenated. The ECMO uses special gas-exchanging membranes for this purpose. The colonization of these membranes with endothelial cells is sought to increase hemocompatibility, thereby reducing complications (e.g. clot formation) and prolonging the duration of use of the gas exchange membranes.

In addition, ECs obtained by reprogramming hiPSCs from patients with pulmonary hypertension may serve as a new relevant in vitro cell culture model to elucidate the underlying mechanisms of disease development.

For these and other future applications, ECs must be provided in large quantities and consistent quality. A research paper authored by the BREATH scientist Ruth Olmer, working group leader at the Leibniz Research Laboratories for Biotechnology and Artificial Organs (LEBAO) of the MHH, published in the journal Stem Cell Reports, recently presented a robust, scalable approach for the efficient differentiation of hiPSCs into ECs. Dr. Olmer was able to show that not only can a large number of ECs be generated with the protocol developed by her working group, but that the cells produced in this way also show all the characteristics typical of these cells and that they can be reproduced in the laboratory over a longer period of time. This protocol opens up new possibilities for a large number of research fields and fields of application, in particular for lung research.

 

Text: BREATH / CD

Picture: MHH / Figiel

 

Dr. Ruth Olmer, Researcher at BREATH and working group leader at the Leibniz Research Laboratories for Biotechnology and Artificial Organs (LEBAO) of the MHH.