CGIDR Stories

How 3D Brain Vessels-On-Chip Can Contribute to Cerebral Malaria Research

Have you ever wondered how close scientists are to being able to grow working organs in a dish? Today, model organs are a reality, and they’re called organs-on-chip. They are engineered devices that mimic the complex structure of organs such as lungs, guts and kidneys. The ability to grow these “mini-organs” has taken off in the last few years with the latest advances in bioengineering that uses technology designed to manufacture computer microchips.

At Seattle Children´s Research Institute, we have recently collaborated with bioengineers at the University of Washington to develop a 3D “brain microvessel model” to study cerebral malaria.

Cerebral malaria is one of the most life-threatening complications of malaria. It is responsible for most of the 400,000 deaths caused by malaria every year. During a cerebral malaria episode, patients – usually children under five years old – lose consciousness, falling into a coma. This occurs because infected red blood cells stick to the brain blood vessels, causing in many cases severe brain swelling and patient death. The only available option for these children is to hope that antimalarials clear their body of parasites quickly enough to indirectly prevent brain swelling – a treatment with a 20% failure rate. If a drug could reverse the brain swelling, the antimalarial drugs would have more time to work, increasing a child’s chances of survival.

That drug doesn’t exist.

To find a cure, malaria scientists have been modelling the complications of cerebral malaria in culture dishes for decades. However, the stiff, flat surface of culture flasks doesn’t bear much resemblance to the human vasculature, where blood vessel cells grow in 3-dimensional tissue structures and are constantly exposed to the blood flow.

3D microvessel modelNew innovative approaches are needed to study this disease complication. The Smith Lab is trying to recreate what happens in the brain of cerebral malaria patients using the 3D microvessel model. The devices, no bigger than the size of a dime, are composed of a scaffold made with collagen, the main structural protein in animal tissues. The collagen scaffold is crossed by tiny tube-shaped holes, simulating the space of a small blood vessel with a diameter approximately the size of a human hair.

In the organ-on-chip, cells that form brain blood vessels create a barrier between the blood (simulated by the open channel) and the tissue (simulated by the collagen). Within a single device, we can simulate the wide range of blood flows present in a healthy blood vessel or a blood vessel affected by malaria parasites. By flowing infected red blood cells through these lab-made tiny blood vessels, we have studied how malaria infected red blood cells stick at different blood flow velocities. We have also demonstrated that different types of malaria parasites respond differently to changes in the blood vessels that occur frequently in cerebral malaria patients.

malaria infected red blood cellsBy better understanding how malaria parasites interact with and damage the blood brain vessels we hope to inspire the design of new drugs that specifically reverse the brain swelling caused by malaria parasites and save thousands of lives.

– Maria Bernabeu Aznar, research scientist, Center for Global Infectious Disease Research