Inner Wheel Australia Foundation Trust success

Every 15 hours a baby is born in Australia with damage to the brain that will result in cerebral palsy (CP). Neuroinflammation is a key driver of damage to the developing brain, either during pregnancy or around the time of birth. Stem cells, particularly from umbilical cord blood (UCB) are shown to protect the brain from injury, but we still do not understand how UCB cells protect the brain from inflammation.

With collaborators in USA, we have developed a human “brain in a dish” that allows investigation of brain development in the laboratory. Our “brain in a dish” provides a high throughput, controlled system of human brain physiology that allows testing of novel therapeutic approaches, like UCB stem cell therapies. We will model neuroinflammation to examine the mechanisms by which UCB cells, and their products (UCB exosomes) modulate an inflammatory environment. This will provide critical information to further develop and optimise the therapeutic benefit of UCB cells.

Aims | Evaluate the effect(s) of UCB cells and their exosomes on inflammation using our “brain in a dish”. Specifically, we will examine- 1) paracrine effects of UCB cells and UCB exosomes, 2) determine the optimum priming of UCB cells to enhance function, 3) identify the transcriptome of brain organoids treated with UCB cells or UCB exosomes.

Hypothesis | UCB cells and exosomes will reduce neuroinflammation in the brain organoid predominantly by modulating trophic pathways and restore functional brain activity. UCB exosomes will provide a novel cell free product to replace UCB cells for therapeutic intervention.

Cerebral Palsy is the most common cause of childhood disability and there is no cure. Parents of children with CP are increasingly seeking stem cells as a therapeutic option. While we know UCB cells can protect the brain from injury, we still do not understand how UCB cells do this and whether their secreted products are therapeutic per-se.We will use our “brain in a dish” experiments to work out how UCB cells or their products protect the developing
brain.