Preclinical study published in Nature Cell Biology, improved cardiac function and reduced scar tissue in laboratory setting

An investigational study of a new cell therapy approach for heart failure has demonstrated human ventricular progenitor (HVP) cells are able to promote the regeneration of healthy cardiac tissue following a heart attack, improve cardiac function and reduce scar tissue.1

The research conducted by scientists at AstraZeneca in collaboration with the Technical University of Munich (TUM), TUM’s university hospital Klinikum rechts der Isar, Karolinska Institutet, and Swedish biotech Procella Therapeutics was published today in Nature Cell Biology.1

The international research team investigated the use of HVP cells, which play a crucial role in formation of the heart during embryonic development, to successfully promote the formation of new cardiac tissue, improve cardiac function and reduce scar tissue in porcine models of acute injury and chronic ischemic heart failure. The results showed a significant reduction in infarct volume of 7.0±1.3% in the HVP treated arm versus 2.5±1.6% in the non-treated arm.1

Karl-Ludwig Laugwitz, Professor of Cardiology at TUM and Head of the First Medical Department Klinikum rechts der Isar, said: “Our research team was able to demonstrate in a laboratory setting how HVP cells can migrate to damaged regions of the heart, mature into healthy working heart cells, while preventing the formation of scar tissue. These findings highlight a significant milestone in the potential therapeutic use of HVP cells in the treatment of patients with serious heart failure, especially amongst older populations for whom heart surgery may represent an excessive strain in recovery.”

Regina Fritsche Danielson, Senior Vice President and Head of Research and Early Development, Cardiovascular, Renal and Metabolism (CVRM), BioPharmaceuticals R&D, said: “These research findings demonstrate the unique capability that HVP cells have in the formation of new cardiac tissue, reducing scar size and importantly improving global cardiac function in pigs with ischaemic heart failure. We are encouraged by these results in HVP cell therapy and the potential of this cell therapy approach in bringing a new wave of cardiovascular treatment to reverse the damage of heart failure, in the future.”

Kenneth R. Chien, Professor of Cardiovascular Research at Karolinska Institutet said: “This is the culmination of two decades of our work to find the ideal cell to rebuild the heart, and provides new hope for the millions of patients worldwide with end-stage heart failure waiting for a heart transplant.”

The research is based on earlier work from the Chien lab that developed large scale production of purified HVPs.2 Further investigations are now ongoing to be able to bring this approach towards the clinic including chemistry, manufacturing and controls (CMC) and toxicology studies. The aim is to start clinical studies within the next two years.

An accompanying Nature Cell Biology News & Views article provides an objective overview of the research.3

Notes

Heart failure
During a heart attack, up to 1 billion heart muscle cells, called cardiomyocytes, may die as a result of reduced blood supply,4 thereby being irreversibly damaged due to their inability to regenerate.5 Damaged cells are replaced by fibrotic scar tissue,6 which is made up of connective tissue, thus increases the rigidity of the heart muscle, reduces its contractile capacity and so can lead to a decline in optimal functioning.5 This can lead to debilitating and often fatal heart failure.4

AstraZeneca in CVRM
Cardiovascular, Renal and Metabolism (CVRM), part of BioPharmaceuticals, forms one of AstraZeneca’s three therapy areas and is a key growth driver for the Company. By following the science to understand more clearly the underlying links between the heart, kidneys and metabolism, AstraZeneca is investing in a portfolio of medicines for organ protection and improved outcomes by slowing disease progression, reducing risks and tackling co-morbidities. The Company’s ambition is to modify or halt the natural course of CVRM diseases and potentially regenerate organs and restore function, by continuing to deliver transformative science that improves treatment practices and cardiovascular health for millions of patients worldwide.

AstraZeneca
AstraZeneca (LSE/STO/Nasdaq: AZN) is a global, science-led biopharmaceutical company that focuses on the discovery, development, and commercialisation of prescription medicines in Oncology, Rare Diseases, and BioPharmaceuticals, including Cardiovascular, Renal & Metabolism, and Respiratory & Immunology. Based in Cambridge, UK, AstraZeneca operates in over 100 countries and its innovative medicines are used by millions of patients worldwide. Please visit astrazeneca.com and follow the Company on Twitter @AstraZeneca.

References
1. Poch C et al. Migratory and anti-fibrotic programs define the regenerative potential of human cardiac progenitors. Nat. Cell Biol. 2022; doi.org/10.1038/s41556-022-00899-8.
2. Foo KS, Lehtinen ML, Leung CY, et al. Human ISL1+ Ventricular Progenitors Self-Assemble into an In Vivo Functional Heart Patch and Preserve Cardiac Function Post Infarction. Mol Ther. 2018 Jul5; 26(7):1644-1659.
3. Timmer LT and van Rooij E. Human ventricular progenitor cells as regenerative cell therapy. Nature News and Views. 2002.
4. Shadrin IY et al. Cardiopatch platform enables maturation and scale-up of human pluripotent stem cell-derived engineered heart tissues. Nat Commun. 2017;28;8(1):1825.
5. Travers JG, Kamal FA, Robbins J, et al. Cardiac Fibrosis: The Fibroblast Awakens. Circ Res. 2016;118(6):1021-1040.
6. Isomi M, Sadahiro T, Yamakawa H, et al. Overexpression of Gata4, Mef2c, and Tbx5 Generates Induced Cardiomyocytes Via Direct Reprogramming and Rare Fusion in the Heart. Circulation. 2021; 143(21): 2123.