There were four aims in the initial proposal: 1) To develop a molecular atlas of the sequential steps of HVP muscle patch formation (implantation/survival, migration, expansion, differentiation, vascularization, matrix formation, and maturation); 2) To examine the effects of defined candidate cues which correlate with muscle patch formation 3) To model cardiomyopathy due to genetic disease, a mutation in phospholamban (PLN), a calcium pump regulator; and 4) To optimize HVP ventricular patch formation to rescue cardiac dysfunction following heart attack.
My lab’s 9 publications are the results of our work revolve around these four goals, and all these publications acknowledges the support of my ERC grant. In short, we have achieved the following:
Aim 1:
• Seminal discovery of human muscle progenitor cells can form muscle patches
• Identified the signature at a single cell level of heart progenitor that can be used for development of heart patch with purifications.
Aim 2
• Identified new pathway that control heart progenitor formation during development in a human culture system.
• New pathways that regulate progenitor expansion unique in human vs. mouse.
Aim3
• Described a human based mRNA model system to identify mutations that cause heart failure.
• Described a novel way to improve the function of heart muscle in the setting of heart failure.
• New technology platform with a combination of mRNA to identify and express nanobodies that can improve heart function.
Aim 4
• HVPs ability to sense and migrate to site of injury in pre-clinical pig model
• Capability of large-scale generation of HVPs
• HVPs can form new muscle patches in the recipient heart, while not contributing to arrythmia.
• Cardiac functional improvement following HVPs treatment in acute and chronic settings.
The recent HVP paper published in Nature Cell Biology (Aim 4) was heavily publicized from press releases (Karolinska Institutet, Technical University of Munich, AstraZeneca), on social media (LinkedIn, Twitter), and announced on Swedish network on gene & cell therapy produces. AstraZeneca have put together a video showcasing the publications and our collaborations, and the video was featured on their homepage. The press coverage in turn was picked up by various news outlets. Scientifically, Nature Cell Biology commissioned a New & Views article on our work to coincide with the publication, and editors across Nature Portfolio put together a special issue which showcases research in stem cells published across different journals, and our HVP paper was selected to be featured in that issue. In summary, we have achieved what we have initially planned for the ERC projects, which is to investigate novel therapeutics to treat heart disease. With the generous support from ERC, we have identified a potential new cell type which is progressing towards the clinic.
