09.05.2019

BREATH researcher develops protocol for generating large quantities of endothelial cells

Endothelial cells (ECs) are involved in various cellular processes, such as 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 and in vitro disease models. Although the isolation of primary ECs from various sources has been demonstrated, the generation of sufficient quantities of cells in stable quality is still a hurdle. Dr. Ruth Olmer has now developed a scalable protocol for the generation of ECs from human induced pluripotent stem cells.

Endothelial cells are involved in various cellular processes, such as 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 and in vitro disease models. Although the isolation of primary ECs from various sources has been demonstrated, the generation of sufficient quantities of cells in stable quality is still a hurdle. Dr. Ruth Olmer has now developed a scalable protocol for the generation of ECs from human induced pluripotent stem cells.

Endothelial cells - specialized, flat cells that line the inside of blood vessels - are involved in various cellular responses. Changes in cell function are associated with a number of pathological processes such as arteriosclerosis, pumping failure of the heart (congestive heart failure) or pulmonary hypertension. Therefore, ECs have been used for a long time as in vitro models to study vascular dysfunction, for example. In addition, ECs are used as important components in tissue engineering. However, the production of sufficient quantities of ECs in consistently very high quality for clinical applications, such as cell therapy, represents a major hurdle. 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 somatic cells and are not only able to multiply indefinitely, but can also differentiate into all cells of the body, including ECs. In addition, reprogramming allows the production of patient- or disease-specific cells.

In lung research, one of the intended applications of ECs is extracorporeal membrane oxygenation (ECMO). In this organ replacement procedure, a machine temporarily takes over the respiratory functions of a patient. Blood is continuously pumped through an oxygenator, which uses membranes to replace the gas exchange in the lungs: carbon dioxide is removed and the blood is enriched with oxygen. In ECMO, special gas-exchanging membranes are used for this purpose. The colonization of these membranes with endothelial cells is intended to increase hemocompatibility and thus reduce complications (e.g. clotting) and extend 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 this and other future applications, ECs must be provided in large quantities and of consistent quality. A paper published in the journal Stem Cell Reports by BREATH scientist Ruth Olmer, group leader at the Leibniz Research Laboratories for Biotechnology and Artificial Organs (LEBAO) at MHH, has now 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 using the protocol developed by her research group, but that the cells produced in this way also exhibit all the properties typical of these cells and can be propagated in the laboratory over a longer period of time. This protocol opens up new possibilities for a variety of research fields and areas of application, in particular lung research.

Text: BREATH / CD