Organ-on-chip technology to study neurodegenerative diseases

Organoids are three-dimensional structures derived from human cells, developed to reproduce the functional, structural, and biological complexity of various human organs in vitro. Although they are the size of a pinhead, their potential is enormous: they can replicate the behavior of heart, brain, or spinal cord tissue, allowing researchers to recreate disease conditions, test therapies and drugs, and predict patient responses. All this can be done much more accurately than with the methods used to date and without resorting to animal models.

The international scientific community has long been working to move beyond animal testing — not only for ethical reasons, but also because results obtained in animal models, such as mice, often fail to translate to humans. Unlike in other Italian regions, animal testing is not permitted in South Tyrol, so for several years the South Tyrolean Institute has been focusing on methods designed to replace animal testing with systems based on induced pluripotent stem cells and now with organoids.

“The first brain organoids we developed relate specifically to the midbrain. They will allow us to study diseases such as Parkinson’s Disease, with a particular focus on understanding the molecular mechanisms underlying this debilitating condition,” explains Francesca Pischedda, a researcher at the Institute of Biomedicine.

At the same time, several researchers are using advanced imaging techniques to analyze both the morphology of the organoids and their activity and in doing so, distinguish between physiological and pathological conditions which could be associated with specific diseases.

To recreate and study some of the characteristics of the original organs, the organoids are engineered at the cellular level and placed on special chips. These chips may include sensors for measuring parameters such as temperature, pH, and oxygen concentration. Alternatively, special microelectrodes integrated directly into the chips can detect the electrical activity of neurons or other electrogenic cells, such as those found in the heart. This methodology allows the behavior of an organoid to be analyzed in a physiological context, as if it were inside a body.

“We’re very proud of the progress we’ve made with this technology. Our institute is one of the few research centers in Italy dedicated exclusively to developing New Approach Methodologies (NAMs) as alternatives and complements to animal testing in preclinical research. We’ve already made significant strides in the field of brain organoids, and other teams are working on organoids that replicate spinal cord and heart tissue,” explains Paolo Cesare, a researcher at the Institute for Biomedicine at Eurac Research.

Organoid research at Eurac Research is also integrated into several projects, including INNo-CHIP, a cross-border collaboration between Italy and Switzerland coordinated by Eurac Research, which brings together 25 partners to develop organ-on-chip prototypes, enhance medical research and the development of new treatments, and stimulate innovation and support for start-ups.

“Organoid research is more than scientific progress; it is a change in the way we imagine medicine. Our organoid research is a fundamental step towards prioritizing Precision Health, a health-centric approach which examines how diseases develop before symptoms appear and which then uses this knowledge to develop targeted, evidence-based prevention strategies with the goal of preserving and improving overall health” says Andrew Hicks, vice head of the Eurac Research Institute for Biomedicine.