Development of a microfluidic "brain-on-a-chip" platform for the study of the physiopathology of immune-mediated diseases.

Abstract

Neurological disorders are the leading cause of disability and the second-largest cause of death worldwide. Despite considerable efforts, neurology remains one of the most challenging areas in terms of understanding the pathophysiology of various neurological diseases due to limitations in investigative methods. Mimicking the complexity of the human nervous system in vitro has proven to be a continuous challenge. In this context, the use of nanobiotechnological resources emerges as a promising alternative for understanding physiological systems.Therefore, the present project proposes the development of a microfluidic "brain-on-a-chip" platform capable of mimicking the complexity of the human nervous system, incorporating key elements such as neurons, microglia, astrocytes, oligodendrocytes, and the blood-brain barrier, for the study of the pathophysiology of immune-mediated diseases. To achieve these objectives,the neuronal microenvironment will initially be established on the "brain-on-a-chip" microfluidic platform, and its functionality will be validated through the assessment of neuronal activity using neurophysiology models. Subsequently, serum samples from patients previously diagnosed with immune-mediated diseases (autoimmune encephalitis or encephalitis associated with anti-MOG antibodies) will be introduced into the functionally validated platform to evaluate neuronal activity after the insertion of patient samples. This device is expected to provide unprecedented results regarding the mimicking of the neuronal microenvironment and how it may be affected in the context of immune-mediated diseases. By creating a system that accurately replicates the structure and function of the human nervous system, the development of a preclinical exploratory model is anticipated. Through a translational and personalized medicine approach, this model aims to translate scientific discoveries into personalized therapeutic approaches more effectively and precisely, benefiting patients in a targeted manner.