To study early stages in embryonic development in the cell culture dish, scientists use so-called human pluripotent stem cells (hPSC). These are cells with have remarkable special properties that can be multiplied as they can indefinitely multiply and are capable of forming any functional cell type of the body.
By applying specific biological or chemical signals, the hPSCs can be directed, for example, be controlled in such a way that they exclusively form pure into heart muscle cells, thereby. These can then specifically grow together to form a tissue – an important tool enabling for the development of new therapies in regenerative therapies to the heart medicine.
Dr. Lika Drakhlis and Dr. Robert Zweigerdt with bioreactors and a special cell culture dish that serves as a platform for growing the hPSC aggregates.
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However, how the many the sequential differentiation of multiple cell types arise step by step during heart development and form the complex organ structures through self-organized formation of complex tissues structures could not be reproduced induced in the cell culture yet dish until now. Now, for the first time, Aa research team led by Dr. Robert Zweigerdt, cell biologist at the Leibniz Research Laboratories for Biotechnology and Artificial Organs (LEBAO) at the Hannover Medical School (MHH), has now achieved this goal. The scientists, for the first time, succeeded in accurately reproducing the complete path to the early stages of a human heart development in a cell culture dish. The research work study has been published in the renowned distinguished journal Nature Biotechnology.
"We cultured grew the hPSCs into as three-dimensional cell aggregates in a hydrogel of proteins and observed the controlled development into so-called heart forming organoids, or HFOs" says Dr. Lika Drakhlis, PhD and first author of the study. In order for the cells to form an early heart stage at all, the scientists had to develop a new differentiation protocol. This special experimental instruction with strategy to direct the exact specifications of the novel for growing the organoid models, which consist of at least seven different highly organized, clearly structured cell- and tissue- types, did not exist for the heart until then. By combining numerous microscopic and molecular methods, the scientists could reveal that HFOs the scientists were then able to show that the cell clumps, which are up to two millimetres in size, develop in exactly the same way as is closely recapitulate key steps known from native known from heart development in the embryo. "At this early stage of development, the organoids consists of three cup-shaped layers, and including’s the anlagen of the heart, the progenitors of for the liver and lungs and the blood vessels, all of which are known to mutually influence each other," explains the first author.
However, these novel findings are not only of interest to the scientific community for elucidating healthy scientist studying organ development. Inherited heart malformations caused by artificial or patients' own genetic defects can now also be studied in the cell culture dish investigated more properly by the HFO strategy. "This is important to better understand congenital heart diseases and then to be able to develop more treat them better appropriate treatments," explains Dr Zweigerdt. In addition, the organoids are suitable for testing pharmacological agents. "The effects efficacy as well as potential side effects of new or further developed established drugs can also be studied more properly in this advanced new model. This in mind, we have just started concrete studies on this set of new studies to further validate and apply the HFO strategy," emphasizes the senior author Robert Zweigerdt study leader.