An international team of scientists made up ofTechnical University of Munich (TUM) and its university hospital Klinikum rechts der Isar, the Swedish Karolinska Institutet, the Swedish biotech startup Procella Therapeutics and the biopharmaceutical company AstraZeneca has studied a way by which the cardiac progenitor cells can form functional heart cells in someone who has been affected by a heart attack.
The results of the Research have been published in the scientific journal Nature Cell Biology.
Cardiac progenitor cells: this is how they work
How can heart function be restored after infatrous? According to the WHO (Health Organization of Humanity) in the world, every year, deaths due to diseases are about 18 million human beings, this is the subject of research all over the world. One possible answer could be treatment with an enriched pool of human pluripotent stem cell-derived ventricular progenitor cells, or HVP for short.
Many heart diseases result in the death of heart muscle cells and blood vessels. This causes fibrotic scar tissue to form, which is responsible for further deterioration of heart function. Some animals, particularly amphibians and fish, can repair such damage, an ability almost entirely absent in the heart of an adult human being.
An experimental approach to restoring lost heart tissue is stem cell therapy. Previous studies have included the use of heart cells grown from stem cells, particularly cardiomyocytes. However, frequent side effects such as irregular heartbeat and fatal arrhythmia have occurred.
In contrast, the research group working with Karl-Ludwig Laugwitz, professor of cardiology at TUM, is studying human ventricular progenitor cells.. These cells play a crucial role in the formation of the heart during development. Over time, they differentiate into the various cell types of the heart, including cardiomyocytes.
Scientists managed to produce large numbers of such HVPs from human embryonic pluripotent stem cells: “This represents the culmination of two decades of our work trying to find the ideal cell to rebuild the heart”he has declared Kenneth R. Chien, Cardiovascular Research Professor al Karolinska Institutet.
Thanks to these cells, it was possible for scientists to study the complex molecular processes involved in the repair of damaged areas of the heart muscle: “In laboratory investigations, we were able to show how HVPs can, in a sense, track down damaged regions of the heart, migrate to injury sites, and mature into functioning heart cells. They also actively prevent scar tissue formation through cross-talking with fibroblasts, as we call the cells that form the structural framework for non-functional connective tissue.“, Said Prof. Laugwitz, who heads the First Department of Medicine of the Klinikum rechts der Isar of the TUM.
For the next step, the interdisciplinary research group used pigs to study the effectiveness of treating a damaged heart with HVP. Physiologically, pig hearts are quite similar to those of humans. As a result, experiments with pigs are often conducted shortly before the start of human patient studies.
The results showed that heart damage can be reliably repaired even in large animals without serious side effects being observed: “The treatment successfully demonstrated the formation of new heart tissue and, above all, the improvement of heart function and the reduction of scar tissue”, explained Dr. Regina Fritsche-Danielson, responsible for research and early development of AstraZeneca.
In the coming months and years, the scientists plan to translate their current progenitor cell research findings to develop a treatment for heart patients. An important intermediate step is the development of hypoimmunogenic HVP lines. Currently, it is necessary to inactivate the recipient’s immune system to prevent it from destroying cell processing.
Hypoimmunogenic cells would eliminate the need for this step, because they would not be identified as foreign bodies to the recipient. Further research will be conducted on hypoimmunogenic cells and possible side effects. The goal is to initiate clinical trials on the therapeutic use of HVPs within the next two years.
“The new insights into the therapeutic use of HVPs represent a milestone in the treatment of several patients with severe heart failure,” concluded Prof. Karl-Ludwig Laugwitz. “Especially patients with coexisting conditions, for whom heart surgery would represent an excessive effort, would benefit from treatment with HVP ”.
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