Human heart cells grown in lab improve heart function in monkeys

Three months after a heart attack, a monkey's heart was beating with the help of cells that began as ordinary blood cells in a laboratory dish. At Hanover Medical School, Ulrich Martin and Robert Zweigerdt have spent more than 20 years trying to repair damaged hearts with cells. Their latest study, published in Nature Communications, reports that the treatment improved heart function after three months in animals.

When a heart attack strikes, the part of the heart muscle that loses its oxygen supply dies, and scar tissue takes its place. The damage can lead to chronic heart failure. The Hanover team does not inject single cells. It injects small clusters of human heart muscle cells, produced in bioreactors from induced pluripotent stem cells, which are adult cells, such as blood cells, reprogrammed to become almost any cell type. The clusters form spherical aggregates, and the team expects more of them to stay in the heart and integrate into the muscle than would be the case with single cells.

The experiments were run with the German Primate Centre in Göttingen, on Javanese macaques in which a heart attack had been induced. Mice were not suitable, because their hearts are much smaller and beat much faster than human hearts. Pigs have hearts closer to ours in size, but their immune systems reject human cells. In monkeys, the human cells grew and survived with appropriate immunosuppressive medication. After three months, extensive new human cardiac muscle fibers had formed. The transplant caused temporary cardiac arrhythmias, but its effect on heart function was positive over time.

The team tested clusters from two iPSC lines, and only those from one of them improved heart function, although both produced grafts of similar size. Zweigerdt suggests that the contraction of the cells in culture is linked to their potential to help the heart, so the contractile force of the clusters should be checked before transplantation. The study does not yet allow conclusions about people, and Zweigerdt says so directly: human cells have their own human heart rate.

For patients, the change would come from the cell source. Current clinical trials worldwide use donor cells, which means immunosuppression for the rest of the patient's life. The Hanover team aims instead to make clusters from each patient's own blood cells, which would avoid that medication and could, in Martin's view, widen acceptance among younger patients, although the approach costs more. The HEAL research project is working to refine the production and delivery of the clusters for human use. The team has not announced a date for human trials, and Martin is clear about the limits: living cells cannot fully heal a heart that is already badly damaged, but they may improve its function.