The study, published in Nature Biotechnology, also shows that there was an effect on driving the formation of a small number of new cardiac muscle cells.
"This is the beginning of using the heart as a factory to produce growth factors for specific families of cardiovascular stem cells, and suggests that it may be possible to generate new heart parts without delivering any new cells to the heart itself ", says Kenneth Chien, a Professor at the medical university Karolinska Institutet in Sweden and Harvard University, US, who led the research team behind the new findings.
The study is based upon another recent discovery in the Chien lab, which was published in Cell Research. This study shows that VEGFA, a known growth factor for vascular endothelial cells in the adult heart, can also serve as a switch that converts heart stem cells away from becoming cardiac muscle and towards the formation of the coronary vessels in the fetal heart. To coax the heart to make the VEGFA, the investigators in the Nature Biotechnology study used new technology where synthetic messenger RNA (mRNA) that encodes VEGFA is injected into the muscle cell. Then, heart muscle produces a short pulse of VEGFA. The mRNA is synthetically modified so that it escapes the normal defense system of the body that is known to reject and degrade the non-modified mRNA as a viral invader.
The study, performed in mice, shows that only a single administration of a short pulse of expression of VEGFA is required, if it can be delivered to the exact region where the heart progenitors reside. The therapeutic effect is long term, as shown by markedly improved survival following myocardial infarction with a single administration of the synthetic mRNA when given within 48 hours after the heart attack. The long-term effect appears to be based on changing the fate of the native heart stem cells from contributing to cardiac fibrotic scar tissue and towards cardiovascular tissue.
"This moves us very close to clinical studies to regenerate cardiovascular tissue with a single chemical agent without the need for injecting any additional cells into the heart." says Professor Chien.
At the same time, he points out that these are still early days and there remains much to be done. In particular, it will become of interest to engineer new device technology to deliver the synthetic mRNA via conventional catheter technology. It also will be critical to move these studies, which are based in mouse models, to other animals, which is currently in progress.
The platform technology is being developed for clinical use by the company Moderna Therapeutics, which was co-founded by Kenneth Chien. A recently announced collaboration with AstraZeneca will support moving the synthetic modified mRNA therapeutics for regenerative cardiology into the clinical setting. This work was also funded with grants from the US National Institutes of Health and The Croucher Foundation, amongst others.
Publication: 'Modified mRNA directs the fate of heart progenitor cells and induces vascular regeneration after myocardial infarction', Lior Zangi, Kathy O Lui, Alexander von Gise, Qing Ma, Wataru Ebina, Leon M Ptaszek, Daniela Später, Huansheng Xu, Mohammadsharif Tabebordbar, Rostic Gorbatov, Brena Sena, Matthias Nahrendorf, David M Briscoe, Ronald A Li, Amy J Wagers, Derrick J Rossi, William T Pu & Kenneth R Chien, Nature Biotechnology, online 8 September 2013, DOI: 10.1038/nbt.2682.
Journal website: http://www.nature.com/nbt
To download images and contact the Press Office: ki.se/pressroom
Karolinska Institutet -- a medical university: ki.se/english
Katarina Sternudd | EurekAlert!
WAKE-UP provides new treatment option for stroke patients | International study led by UKE
17.05.2018 | Universitätsklinikum Hamburg-Eppendorf
First form of therapy for childhood dementia CLN2 developed
25.04.2018 | Universitätsklinikum Hamburg-Eppendorf
The more electronics steer, accelerate and brake cars, the more important it is to protect them against cyber-attacks. That is why 15 partners from industry and academia will work together over the next three years on new approaches to IT security in self-driving cars. The joint project goes by the name Security For Connected, Autonomous Cars (SecForCARs) and has funding of €7.2 million from the German Federal Ministry of Education and Research. Infineon is leading the project.
Vehicles already offer diverse communication interfaces and more and more automated functions, such as distance and lane-keeping assist systems. At the same...
A research team led by physicists at the Technical University of Munich (TUM) has developed molecular nanoswitches that can be toggled between two structurally different states using an applied voltage. They can serve as the basis for a pioneering class of devices that could replace silicon-based components with organic molecules.
The development of new electronic technologies drives the incessant reduction of functional component sizes. In the context of an international collaborative...
At the LASYS 2018, from June 5th to 7th, the Laser Zentrum Hannover e.V. (LZH) will be showcasing processes for the laser material processing of tomorrow in hall 4 at stand 4E75. With blown bomb shells the LZH will present first results of a research project on civil security.
At this year's LASYS, the LZH will exhibit light-based processes such as cutting, welding, ablation and structuring as well as additive manufacturing for...
There are videos on the internet that can make one marvel at technology. For example, a smartphone is casually bent around the arm or a thin-film display is rolled in all directions and with almost every diameter. From the user's point of view, this looks fantastic. From a professional point of view, however, the question arises: Is that already possible?
At Display Week 2018, scientists from the Fraunhofer Institute for Applied Polymer Research IAP will be demonstrating today’s technological possibilities and...
So-called quantum many-body scars allow quantum systems to stay out of equilibrium much longer, explaining experiment | Study published in Nature Physics
Recently, researchers from Harvard and MIT succeeded in trapping a record 53 atoms and individually controlling their quantum state, realizing what is called a...
25.05.2018 | Event News
02.05.2018 | Event News
13.04.2018 | Event News
25.05.2018 | Event News
25.05.2018 | Machine Engineering
25.05.2018 | Life Sciences