ESPOIR

European clinical study for the application of regenerative heart valves

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 Obiettivo del progetto (Objective)

'Acquired and congenital heart disease can necessitate heart valve replacement. However, current heart valve substitutes are not considered ideal as they need anticoagulation, bearing the risk of bleeding when manufactured from non-organic material, or they degenerate when they derive from animals or human tissue donators (homografts) thereby leading to frequent reoperation especially in the young population. An ideal heart valve substitute would overcome these limitations and even have the potential to grow when implanted in pediatric patients.

Haverich et al. have developed an implant for heart valves, which is better tolerated than the known alternatives and which has the potential for regeneration by autologous recellularization. Implants derive from donated homografts, which are chemically treated to inactivate potential microorganisms and viruses. The heart valves then are decellularized chemically, so that only connective tissue remains, the matrix of the decellularized heart valve (DHV). DHV has been examined in extensive animal studies, including immunological and toxicological analysis, long term and growth models, all of which have shown that the implant is well tolerated and spontaneously recellularized by the recipient.

The proposed ESPOIR project is based on auspicious early clinical results in 45 children and young adults. In order to drive translation of this promising regenerative approach towards practical clinical use and to reduce the burden of congenital heart defects in particular, the ESPOIR consortium will undertake a prospective multi-centre trial to include at least 200 patients from 8 leading European Centres for Congenital Heart Surgery, for robust statistical evaluation of DHV in direct comparison to conventional heart valve substitutes.'

Introduzione (Teaser)

A European consortium is putting a novel regenerative human heart valve to the test that may revolutionise the field of cardiovascular tissue engineering. Based on a special technology that removes all biological material from the valve, this novel medical product boasts immune tolerance and longevity.

Descrizione progetto (Article)

Heart valve transplantation is the gold standard for treating acquired and congenital valvular heart disease. Immune compatibility issues are a major problem with most grafts, and for young patients the graft needs to be able to grow with the patient. Usually, mechanical or biological valves are used, which are associated with undesirable effects such as clotting and degeneration.

Previous work by the consortium partners has resulted in the development of human-donated decellularised heart valves that have been treated to remove all biological material. The collagen matrix that is essentially left behind forms an excellent scaffold for autologous cells to grow into a new valve.

Preliminary data in paediatric and adolescent patients indicate great immune tolerance of the decellularised heart valves. So far, none of the transplanted patients have rejected the valves nor required a reoperation.

The EU-funded 'European clinical study for the application of regenerative heart valves' (http://www.espoir-clinicaltrial.eu (ESPOIR)) project hopes to recapitulate these promising results in a four-year clinical trial. The consortium comprises eight leading paediatric cardiac surgical centres across Europe that aim to operate on over 200 patients during the trial. The European Homograft Bank, the German Society for Tissue Transplantation (DGFG) and other cooperating tissue banks will provide the heart valves and the decellularisation process will be carried out by a collaborating small enterprise.

The consortium has mainly concentrated on setting up protocols for defining and ensuring quality standards of non-cryopreserved homografts as well as the decellularisation process. An advanced database infrastructure has been implemented for long-term storage of data generated during ESPOIR. A patient registry containing data on 98 pulmonary valve implantations in children, adolescents and adults has also been generated.

The ESPOIR decellularised heart valve is envisioned to last up to 20 years, significantly reducing the need for reoperation. This will not only cut back on heart valve reoperation costs, but also substantially improve the quality of life of operated patients by minimising side-effects.