Pioneering stem cell therapy at Bristol Royal Hospital for Children

Dr Filippo Rapetto discusses an innovative case using donor stem cells which offers hope for babies born with heart problems.

FinleyFilippo, can you tell us what happened?

Finley was four days old when he was diagnosed at Bristol Royal Hospital for Children with transposition of the great arteries, which affects about one in 3,000 newborns. The treatment, which is very well established, is an operation called arterial switch procedure, which includes a complex surgical step called coronary artery translocation. Unfortunately, in this case, one of the coronary arteries had an anomalous course and the translocation was not successful. This caused a significant deterioration in Finley’s cardiac function.

We struggled for a couple of months with various treatments, such as extra corporeal membrane oxygenation (ECMO). After we managed to wean him off that, he was still in intensive care for many weeks, dependent on inotrope drugs to increase his heart function, which was very poor.

Because there was no conventional way to treat his condition, Professor Massimo Caputo with the Paediatric Cardiac Surgery team, the Paediatric Cardiology team and the Paediatric Intensive Care team, suggested we source donor mesenchymal stromal cells (stem cells) to inject directly into Finley’s heart with a second surgical procedure. We have a collaboration with the Centre for Cell, Gene and Tissue Therapeutics (Royal Free Hospital, UCL) which provided us with the cells within a few days. Professor Caputo managed to get compassionate funding from the Trust, and he got the process going quickly.

Following the procedure, we noticed a slow but consistent improvement in the patient’s clinical conditions. We then did multiple echocardiograms to monitor the cardiac function, and it got gradually and consistently better. He was able to go home about three months after the stem cell injection.

Has he made a full recovery?

He started from what we call a severe dysfunction and now his heart function is close to normal, comparable with someone who had a heart operation as a newborn.

What evidence do you have that the procedure worked?

From a scientific point of view, the only way to know whether this procedure helped would be to take some of the patient’s myocardium (muscular tissue of the heart) and analyse it, which clearly we cannot do, but the clinical change after the injection was impressive. This stem cell injection technique is not something that we invented, but this case is the first in the world that we know of, for this condition, at this age, in a patient with established cardiac dysfunction (rather than as a preventive measure), and with donor stem cells rather than previously collected cells from the patient.

How difficult is it to find a match from donor stem cells?

One of the criticisms made about this approach in the past is that there is a potential risk of triggering an immune response, but this has been shown not to be the case. No complex immunological matching is needed to utilise the cells, as they don’t necessarily have to survive in the patient for a long time. The hypothesis is that they promote the recovery of the patient’s own tissues by acting as modulators of the patient’s healing processes.

Once we took the decision to try this procedure, then everything happened pretty quickly, and that’s the beauty of it. Because he was getting worse, we didn’t have the possibility of isolating their own cells and making them grow to obtain a sufficient dose – he was too unwell.

Was there an alternative?

In desperate cases like this one, you could go to urgent transplantation, but it’s very difficult to find a heart for a newborn because there are very few donors. Also, this happened in the middle of the first lockdown, when the transplantation service had pretty much stopped all over the country, for nearly all patients, so this wasn’t an option.

Stem cell treatment is not the codified, recognised treatment, whereas transplantation is, so we had a discussion with several transplant centres. But I think the chances of finding a heart in time, and ultimately the chances of a good outcome, would have been minimal if we had waited longer.

What’s the next step in the research?

This case is important because it demonstrates that cells that are not autologous (that come from different individuals) are safe to use. There are a lot of patients with other congenital heart conditions that could potentially benefit from this concept, so this is extra evidence that stem cell therapy has potential.

Might this technique become a standard way of treating these kinds of conditions?

With Professor Caputo’s research group, we already use similar stem cells in our animal research projects, and we are trying to translate their use from animals to humans. There are several common congenital heart defects, which require some sort of surgical valve and/or vascular replacement with prosthetic materials, but these materials don’t grow or repopulate with the patient’s tissues. We want to reduce the rate of replacement, so we are trying to merge the currently available materials with stem cells to create a more biologically compatible tissue to be used in children.

We are delighted that Professor Caputo has been awarded a three-year BHF Translational Award to take this research to the next stage. If a subsequent clinical trial shows that the therapy is effective, this new treatment could potentially avoid repeated high risk and stressful heart operations, and significantly improve quality of life for many children living with congenital heart disease.

Read the case report

Allogeneic Mesenchymal Stromal Cell Injection to Alleviate Ischemic Heart Failure Following Arterial Switch Operation‘ by Filippo Rapetto, Demetris Taliotis, Qiang Chen, Iakovos Ttofi, Dominga Iacobazzi, Paolo Madeddu, Serban C. Stoica, Ben Weil, Mark W. Lowdell, and Massimo Caputo, in JACC: Case Reports

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