3D human brain cell models: New frontiers in disease understanding and drug discovery for neurodegenerative diseases

Abstract

Neurodegenerative disorders have an enormous impact on society and healthcare budgets. There has been a high degree of failure in many recent clinical trials for disease-modifying therapeutics. A major factor in this failure is the difficulty of translating findings from animal-based cell models to human patients. The majority of non-animal neurodegenerative disease research has been conducted in 2 dimensional models of rodent neonatal neurons and glia. While these systems have provided valuable insights into neural cell function and dysfunction, they have largely reached the end of their useful life, as human stem cell technologies combined with major advances in microfluidic technologies have opened the door to development of patient-derived 3D brain cell models. These have major advantages in providing a micro-physiological system more closely reflecting the in vivo brain environment, and promote the interaction between different patient-derived brain cell-types. However, major challenges remain before these model systems will replace the 2D rodent models as the workhorse for neurodegenerative disease studies. Despite these challenges, we are likely to experience a rapid transition of research from old models to new patient derived 3D brain cell systems, which will likely improve translational outcomes for disease therapeutics.