BEIJING, May 18 (Xinhua) -- Chinese researchers have successfully engineered a "biological pacemaker" in a petri dish, creating a sinoatrial node organoid that can be regulated by nerve cells to control the heartbeat, a breakthrough that offers a new platform for studying heart rhythm disorders and drug development.

The heart's continuous and rhythmic beating relies on the "natural pacemaker" in the right atrium -- the sinoatrial node. It continuously generates electrical signals under nervous system control and coordinates the atria and ventricles through the cardiac conduction system to contract in unison, pumping blood throughout the body. Should the sinoatrial node fail, the heartbeat might slow down or even stop, which can be life-threatening in severe cases.

The sinoatrial node is extremely small and deeply concealed, making it difficult to obtain human samples. Animal models such as mice fail to accurately simulate the human heartbeat or the neural regulation of cardiac rhythm.

How to create a near-authentic human "biological pacemaker" in the laboratory has long been a major challenge in cardiac pacing and conduction research.

By simulating key signals in embryonic development and conducting systematic screening, researchers from institutions such as the Center for Excellence in Molecular Cell Science of the Chinese Academy of Sciences and Zhongshan Hospital of Fudan University guided stem cells to form three-dimensional sinoatrial node organoids capable of autonomously generating stable heartbeats.

When connected to atrial-like organoids, electrical signals could be emitted from the sinoatrial node and conducted to the atrial tissue, thereby successfully mimicking the in vivo "pacing-conduction" process.

They further explored the mechanisms underlying cardiac arrhythmias. After introducing mutations associated with familial sinoatrial node dysfunction into the organoids, the "pacemaker" beat significantly slower, thereby recapitulating key features of bradyarrhythmia.

Medical treatment ameliorated the abnormal rhythm, demonstrating that this model can not only elucidate the mechanisms underlying heart rate-related diseases but also be used to evaluate potential therapeutic agents.

In a real heart, the nerves surrounding the sinoatrial node regulate heart rate in response to the body's condition. To simulate this process, the researchers constructed neuron-rich cardiac ganglionated plexus organoids and assembled them with sinoatrial node organoids and atrial organoids.

The experimental results showed that nerve fibers could extend into the sinoatrial node organoids, regulate their beating frequency, and conduct electrical signals to the downstream atrial tissue.

The study has been published in the journal Cell Stem Cell. ■