Cardiovascular Moonshot (RegMed XB)

2018

Heart failure is a global public health issue with a largely equal distribution between men and women. For patients with end-stage heart failure limited treatment options are available. The Cardiovascular Moonshot of RegMed-XB (CMRM-XB) is a comprehensive program based on the concept of developing personalized cardiac regenerative therapies tailored to individual patients. The researchers aim to enhance the body's inherent regenerative capacity, such as improving contractility and perfusion of the heart muscle, repairing or replacing coronary arteries and heart valves. Importantly, researchers will gain insights into optimizing heart treatment and potentially preventing certain cardiovascular diseases in patients.

The Research
The research is focused on the creation of  a(n) (additional) solution(s) for patients by regenerating the human heart inside (in-situ) or outside of the body (ex-situ). Repair of the heart in a cardiac perfusion bioreactor (ex-situ) offers unique opportunities, including the possibility to  apply treatments without off-target effects to distant organs or wash-out of therapeutics. Initially, this could be an option to restore donor hearts for transplant recipients. After restoring the heart, it will be re-implanted. This strategy also facilitates exploration of gene therapy for hereditary diseases. Along this process, the researchers learn how to treat the heart better and eventually also aim to deduce how to treat the heart inside a patient.

The Cardiovascular Moonshot of RegMed XB is the most recent addition to the Moonshot initiatives. To date, it has completed a hypothermic pilot study that has enhanced researchers' expertise in perfusion models. Currently, this model is undergoing further refinement for optimal heart preservation. Additionally, ongoing histopathological analysis of heart valves aims to elucidate how these valves remodel in response to altered fluid dynamics within the ex vivo heart platform.

The cardiovascular Moonshot consists of a multidisciplinary team of transplant surgeons (Utrecht), cardiologists (Utrecht, Maastricht), engineers (Eindhoven) and biologists (Leiden) with the support and input of key stakeholders including patients and companies.

The origin

RegMed XB is a virtual institute that currently comprises Dutch and Belgian public (universities and governments) and private (health foundations and companies) partners that work together to develop regenerative medicine solutions. Regenerative medicine aims to restore degenerated, diseased, or damaged tissues and organs, thereby increasing vital functioning and reducing the cost of healthcare. RegMed XB collaborates on ambitious projects in the field of regenerative medicine. Initially, five health foundations have joined the TKI-program by Health~Holland to define the research objectives and co-govern the projects. Numerous companies have joined and the regional governments support both the research and its valorisation.

The cardiovascular Moonshot recently received follow-up funding from the Dutch Heart Foundation through the Open PSS program, which the Dutch Heart Foundation receives from Health~Holland. In addition, companies involved are also making a financial contribution; these are Coagulation Profile and Axion Biosystems.

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Contact person:

Prof. Dr. P. Doevendans (Pieter)

Principal investigators

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National Network Healthy Living in a Healthy Environment

2022
Promoting a healthy lifestyle and maintaining it for a long time is crucial for the prevention of cardiovascular diseases. Lifestyle change areonly sustainable and impactful if it takes into account the context in which it occurs. The research Therefore, this netwerk will disseminate this insight widely to policymakers, researchers and everyone who contributes to promoting healthy behaviors. In this way, we can collectively achieve greater health gains when implementing potentially successful interventions. The ultimate goal is to achieve sustainable and impactful lifestyle change in the population. In the projects LIKE, BENEFIT and SUPREME NUDGE, unique expertise has been gained in the field of (1) embedding lifestyle interventions in complex systems, and (2) changing systems underlying lifestyle behavior. Within this national network, we want to disseminate and embed this expertise among researchers, practice professionals and policy makers. We will combine this expertise in the form of two toolboxes; a toolbox for practice professionals and policy makers and a toolbox for researchers. To this end, existing tools will be adapted, where necessary, to make them more widely usable. We aim to embed the toolboxes in (existing) structures and will make the toolboxes findable and disseminated through this netwerk. This network will serve as a structure for connections between stakeholders and contribute to the realization of a sustainable knowledge infrastructure. With this project we identify and create important conditions for successful further development and upscaling of innovative and sustainable ways to sustain healthy living for longer. With this we go further than many existing networks and knowledge infrastructures that focus only on 'effective interventions' but not on the structural embedding in systems or addressing the systems themselves. The origin From 2017, the Dutch Heart Foundation, together with ZonMw, invested in research by three healthy living consortia (LIKE, BENEFIT and SUPREME NUDGE). The common goal was to find new ways to achieve sustainable and impactful lifestyle change in the population. Heart Foundation and ZonMw asked the three healthy living consortia Supreme Nudge, LIKE and Benefit to join forces within this theme by using the knowledge they have gained over the past few years. Although the three consortia each had a different approach, the research leaders agreed on what is needed for lifestyle change to be truly successful: a shift in thinking about lifestyle change. Subsequently, the Dutch Heart Foundation and ZonMw provided follow-up funding to join forces and acquired knowledge in a new knowledge infrastructure.
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Holland Hybrid Heart

2023
In the Netherlands, there are 250,000 patients with heart failure. Half of these patients die within five years. The best treatment: a donor heart. But: there is a great shortage of these. The Holland Hybrid Heart consortium is therefore working on an alternative: a robot heart, made of soft materials. The research We envision the treatment of patients with heart failure (HF) in such a way that the survival and quality of life of HF patients drastically increases. We aim to achieve this by developing a unique bioinspired total artificial heart that integrates soft robotics and tissue engineering (TE). In the long term, we foresee that this pioneering technology allows us to develop and bring to the clinic a full set of artificial motile organs and tissues that seamlessly integrate with the human body. This will be possible as the novel and exciting technologies underlying the artificial heart developed in this project - soft robotics and in situ TE - can be used to generate a broad range of artificial motile organs such as muscle structures (e.g., limbs), bowels or lungs: The motility and flexibility in shape and size of soft robots make them suitable for mimicking motile organs. Actuators can be embedded within the elastomeric matrix of these robots without compromising their malleable properties. In addition, embodied intelligence provides direct feedback on shape and force, enabling natural behaviour. Biocompatibility of these artificial organs is provided by TE inside the body (in situ) using biodegradable coatings or scaffolds. Such TE scaffolds are cell-free synthetic bio-resorbable implants or linings that can recruit or interact with cells from the bloodstream, leading to gradual replacement of the scaffold by fully endogenous, and thus biocompatible, tissue. Importantly, the cell-free and thus off-the-shelf availability of these scaffolds avoids the high costs and complex logistics inherent to pre-implantation in vitro TE. The Holland Hybrid Heart (HHH) consortium will push the development of these newly emerging technologies forward and combines soft robotics and in situ TE to generate the first biocompatible, soft actuated heart. This project will deliver Proof-of-Principle for full in vivo cardiac functionality of the artificial HHH in large animals. If successful, the HHH will be available for translation to the clinic as an effective treatment for advanced HF in patients and a valid alternative for moderately effective current HF therapies. This is a quantum leap forward in the treatment of HF. Origin A photo in the newspaper inspired Rotterdam heart specialist Jolanda Kluin to develop a robot heart. Kluin immediately contacted the interviewee in the article, Bas Overvelde, head of the Soft Robotic Matter group at Amolf, which develops soft robots. Could he perhaps also make a heart using soft robot techniques? Overvelde believed in it and a collaboration was born. Five years ago, they received a European subsidy of more than 3 million euros. This grant started the previous EU consortium, the EU Hybrid Heart. Last December (2023), Kluin received another 11 million euros from the Dutch government to continue the Holland hybrid heart project. The Holland Hybrid Heart has pivoted to meet the demands of that new grant and now only contains 15 Dutch consortium partners. The consortium is funded by NWA-ORC and the Dutch Heart Foundation. In-kind contributions are also provided by the DCVA, the Dutch Heart Foundation, TrailBlazers, SBMC, EVOS and EE-Labels. The executing academic partners are Erasmus MC, Amolf, TU Eindhoven, University of Twente, TU Delft and Saxion Applied University. This research is driven by patient needs and the Harteraad and Stichting Pulmonale Hypertensie will provide the connections to these patients.
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