Background

Perinatal brain injury happens around the time of birth, often when the brain is deprived of oxygen and blood, and it can affect a child for life.

One possible treatment uses extracellular vesicles, tiny packages that cells release to send signals to other cells. Those released by stromal cells from Wharton’s jelly, the tissue inside the umbilical cord, reduce inflammation and aid recovery in animal studies. Whether they do the same in a human brain is a harder question, because a newborn human brain is not a rodent one.

The Prenatal Medicine Laboratory at the University of Bern has built a human alternative. Starting from reprogrammed human stem cells, they grow cerebral organoids, three-dimensional tissue that develops the cell types, architecture and electrical activity of a developing brain. Oxygen deprivation and inflammation can be simulated in these organoids, and the vesicles tested on them directly.

What the lab could not do was measure whether the tissue recovered its function. An organoid can look repaired without working. Answering that means recording the electrical signals passing between neurons, and the lab’s existing method, which tracks calcium as an indirect signal, is too slow and too coarse.

High-density multielectrode arrays solve it. The organoid sits on a chip carrying thousands of electrodes, which pick up the activity of individual neurons, millisecond by millisecond, and show how the network is connected. Nothing is inserted into the tissue and no dye is needed, so the same organoid can be recorded repeatedly as it changes.

Simona Lodato’s group at Humanitas University in Milan works on how neural circuits form, and uses this technique on cortical organoids. This grant funded two weeks there.

Aims

• Learn to record from cerebral organoids using high-density multielectrode arrays, from preparing the organoid on the chip through to acquiring the data.
• Learn to analyse the recordings, including patterns of network activity and how neurons are connected.
• Apply the technique to organoids that have been injured and then treated, to test whether function actually returns.
• Establish the method in Bern and write a protocol and troubleshooting guide for the lab’s own organoid system.