New EU-funded project trials novel type of graft for replacement of aortic valves

The EU-funded project ARISE is trialing a novel type of graft for the replacement of aortic valves: it is using donated human heart valves that have been stripped of the donor’s cells to appease the recipient’s immune system.

The partners involved in the project expect their decellularized grafts to offer a more durable solution than other biological implants, which typically have to be replaced after a number of years and tend to deteriorate faster in this age group than they might in older recipients.

Approximately 65 000 aortic heart valve replacements are carried out in Europe per year, of which nearly 10 % are repeat operations, the ARISE team notes. Biological grafts that last longer could significantly improve patients’ quality of life and reduce the cost to healthcare systems.

The partners had previously trialed decellularized grafts in predecessor project ESPOIR, which focused on the replacement of pulmonary heart valves. The procedures carried out by the two projects are recent and don’t, as yet, yield insight on the performance of the grafts over longer timeframes, says Samir Sarikouch of Hannover Medical School, who directed both trials.

However, the partners do have data on a number of cell-free pulmonary valve grafts they implanted prior to these projects. These figures reflect near-total freedom from reoperation during the 10 years following implantation, Sarikouch reports. This outcome compares very favorably to the 84 % and 82 % respectively achieved by conventional human valve grafts or grafts of bovine origin, he notes.

Grafts for a new generation

Sarikouch’s conclusion is clear: in his opinion, the partners’ cell-free implants are by far the best option for the targeted age group. In Austria, Germany and Switzerland, they are already available through the national healthcare systems, and evaluations are under way in Belgium and the Netherlands, he adds.

The reason why conventional biological grafts tend to break down faster in younger recipients is that these patients’ immune systems are generally stronger than those of older individuals, Sarikouch explains.

Biological grafts are not the only option open to patients, as mechanical valve prostheses do exist. However, says Sarikouch, these devices require recipients to take blood thinners, which can limit them in their choices.

To explain, he notes that mechanical implants are not, for example, a good option for women planning to start a family, as they involve added risk to the expectant mother and to the unborn child.

Pumping for progress

The partners’ cell-free grafts are designed to provide recipients with a better chance of leading perfectly normal lives, Sarikouch observes. All that remains after decellularization is the matrix of the graft – a structure consisting of mainly of collagen that is less visible to the immune system.

Once the graft is implanted, the organism populates it with cells of its own, Sarikouch adds. ‘We hope that, as a result of the process, the graft will be integrated into the body and last much longer – maybe even a whole lifetime,’ he says.

It’s pioneering work, in more ways than one. The partners’ grafts turned out to pose a challenge in terms of their classification that complicated approval processes not only for their use, Sarikouch notes, but also for crossborder shipment of the valves – with implications for the organization of the trials, which involve hospitals in several countries.

This difficulty encountered in ESPOIR was addressed in cooperation with the relevant authorities in these various countries, all of which have different and highly specific rules regarding human-derived products, says Sarikouch.

‘In ARISE, we are building on the experience we have gained, but also on the experience the authorities have gained,’ he says.

A path through this new regulatory territory having been mapped, the partners hope that it will benefit regenerative medicine in general by facilitating the handling of authorization requests.

The processes governing tissue donations – on which the partners rely for their grafts – also differ significantly from one country to another, Sarikouch notes, underlining the need for communication and effective coordination to ensure that opportunities to help are not wasted.

The donation of a heart may, for example, not automatically imply that parts may be used if the organ cannot be implanted as a whole, he points out. And yet, families gifting a loved ones’ heart to save another person’s life are unlikely to be concerned about this distinction, he adds.

Meanwhile, in ARISE, the work continues. The trial is to involve 120 patients, of which 114 have already received their cell-free grafts, Sarikouch reports. They will be followed up over a period of 10 years, although the project itself will end in March 2019.