Researchers at Karolinska Institutet, Technical University of Munich (TUM) in Germany and AstraZeneca, among others, have identified a new type of cell therapy with the potential to heal injuries to the heart after a heart attack. The preclinical study, published in the journal Nature Cell Biology, shows that so-called ventricular progenitor cells can stimulate the heart’s repair ability and reduce scar tissue.

This is the culmination of two decades of work to find the optimal cell to repair a damaged heart. The results mean new hope for the millions of patients with heart failure around the world who are waiting for a heart transplant, says Kenneth Chien , senior professor at the Department of Cell and Molecular Biology at Karolinska Institutet and one of the study’s authors.

The study was also conducted in collaboration with researchers at TUM’s University Hospital Klinikum rechts der Isar and Procella Therapeutics.

In a heart attack, millions of heart muscle cells (cardiomyocytes) die due to reduced blood flow. These are replaced by fibrotic scar tissue, which further impairs the heart’s ability to pump blood around the body. This in turn can lead to heart failure, a common and often fatal condition that affects more than 60 million people globally.

Unlike during fetal development and in young children, the adult heart’s ability to form new heart muscle cells is very limited. Many researchers are therefore interested in the possibility of using cell therapy to stimulate the heart’s regenerative ability. Previous studies have partly focused on mature cardiomyocytes, but side effects such as heart rhythm disorders have so far prevented clinical use.

HVP cell therapy

– In laboratory studies, we saw how the HVP cells migrated to damaged regions of the heart where they then matured into healthy functioning heart cells and counteracted the formation of scar tissue. The results represent an important milestone in the work of finding a possible treatment with HVP cells for patients with severe heart failure, especially for the elderly where heart surgery would be a great strain, says co-author Karl-Ludwig Laugwitz , professor of cardiology at TUM.

Also in animal studies, the researchers saw a clear improvement in cardiac function in pigs injected with HVP cells after an injury compared to the untreated group. During the follow-up period of three months, no tumor formation was seen, which is promising for any future clinical studies.

New formation of heart tissue

– The results indicate a unique ability of HVP cells to regenerate heart tissue, reduce scar tissue and improve heart function in pigs with ischemic heart failure. We are encouraged by these results in HVP cell therapy and the possibility of finding new cardiovascular treatments in the future to counteract heart failure injuries, says Regina Fritsche Danielson , head of research and early development in the field of cardiovascular, kidney and metabolic diseases at AstraZeneca.

In a next step, the researchers plan to carry out, among other things, toxicological studies and investigate the possibility of developing cell lines that are tolerated by the immune system. At present, treatment with immunosuppressive drugs is required to prevent the immune system from rejecting transplanted HVP cells. The hope is to begin clinical trials within the next two years.

This project has received funding from the European Research Council (ERC) under the European Union’s research and innovation program Horizon 2020 (grant number 743225), the Swedish Research Council, the German Research Foundation, Transregio Research Units 152 and 267 and DZHK. Several of the study authors are employed by Procella Therapeutics, which owns the intellectual property rights to the HVP technology, or by AstraZeneca. Kylie Foo and Kenneth Chien are inventors of a patent based on HVP technology.

Publication

” Migratory and anti-fibrotic programs define the regenerative potential of human cardiac progenitors ,” Christine M. Poch, Kylie S. Foo, Maria Teresa De Angelis, Karin Jennbacken, Gianluca Santamaria, Andrea Bähr, Qing-Dong Wang, Franziska Reiter, Nadja Hornaschewitz, Dorota Zawada, Tarik Bozoglu, Ilaria My, Anna Meier, Tatjana Dorn, Simon Hege, Miia L. Lehtien, Yat Long Tsoi, Daniel Hovdal, Johan Hyllner, Sascha Schwarz, Victoria Jurisch, Marcella Sini, Mick D Fellows, Matthew Cummings , Jonathan Clarke, Ricardo Baptista, Elif Eroglu, Roland Tomasi, Andreas Dendorfer, Marco Gaspari, Giovanni Cuda, Markus Krane, Daniel Sinnecker, Petra Hoppmann, Christian Kupatt *, Regina Fritsche Danielson *, Alessandra Moretti *, Kenneth R. Chien *, and Karl-Ludwig Laugwitz *, Nature Cell Biology, online May 12, 2022, doi: 10.1038 / s41556-022-00899-8