REANIMA: toward a new paradigm in cardiac regeneration

Endogenous mechanisms of tissue regeneration provide an innovative research avenue in the cardiac regeneration field. The topic is also the central area of interest of the REANIMA project, a research programme involving twelve European research centres, including the IMP. The project, which is coordinated by the Centro Nacional de Investigaciones Cardiovasculares (CNIC) in Madrid, will be supported by €8 million funding from the European Commission over a period of 5 years. It will launch in January 2020.

Cardiovascular disease is the leading cause of death in the world. Heart failure is a worldwide epidemic that imposes a heavy societal burden in death, disease, and escalating economic costs. 

The inability to regenerate heart muscular tissue lost during a heart attack is the major factor in a high proportion of cases of heart failure. To resolve this problem, the goal of REANIMA (New-generation cardiac therapeutic strategies directed to the activation of endogenous regenerative mechanisms) is to provide new therapies for heart regeneration.

Until now, clinical trials based on the introduction of stem cells into the heart have not shown regenerative capacity. However, studies of spontaneous and induced heart regeneration in animal models suggest that the path to progress lies in the reactivation of endogenous regenerative mechanisms. Fish and amphibians are able to regenerate their hearts, and although mammals have historically been considered to lack this capacity, regeneration was recently shown to occur in injured hearts of newborn mice. Unfortunately, in adult mammals, including humans, the heart’s residual capacity to regenerate is insufficient to recover function naturally.

“REANIMA will exhaustively analyse knowledge accumulated from research in animal models in order to transform it into new regenerative therapies to resolve heart failure”, according to coordinator Miguel Torres. The project brings together knowledge obtained from species that can regenerate their hearts (fish and amphibians), animals that cannot (adult mammals), and human heart tissues generated by tissue engineering. 

Elly Tanaka, a Senior Scientist at the IMP, is one of the partners in the consortium. Her group uses the Mexican salamander axolotl as a regenerative model organism. The scientists will investigate which genes are turned on in the regenerating axolotl heart and compare the results to mouse and human samples to understand how to avoid scarring and promote heart regeneration. The work-package at the IMP will receive 780,000 Euro out of the total 8 million.

“I am excited to work with this consortium of outstanding scientists to understand how axolotls and zebrafish regenerate their heart and to attempt to use the knowledge to promote regeneration in large animal models”, says Elly Tanaka. 

REANIMA was selected for funding in the “Regenerative medicine: from new insights to new applications” call, published within the “Health demographic change and wellbeing” H2020 Work Programme. This call had a total Budget of €50,000,000 and received 154 project submissions. REANIMA was the second ranked project and received the maximum permitted funding, a total of €8 million for 12 European institutions in several countries and covering a period of 5 years.

REANIMA is the first Europe-wide project to integrate basic research findings in an effort to transform them into medical applications in the field of cardiac regeneration. REANIMA is funded by the European Union's Horizon 2020 research and innovation programme under grant agreement nº 874764. Project activities range from identifying new targets in animal models to the design of clinical trials. In addition to the CNIC and the IMP, another ten European centres participate in the project: Universitätsklinikum Hamburg-Eppendorf, UKE (Germany); King's College London (UK); University of Bern (Switzerland); the Weizmann Institute of Science (Israel); Hubrecht Institute (the Netherlands); Ethris GMBH (Germany); ZeClinics SL (Spain); German Primate Center, DPZ (Germany); Scuola Superiore Sant' Anna (Italy), and the Fraunhofer Institute for Cell Therapy and Immunology IZI (Germany).