A Long-Living Bioengineered Neural Tissue Platform to Study Neurodegeneration

Abstract

The prevalence of dementia and other neurodegenerative diseases continues to rise as age demographics in the population shift, inspiring the development of long-term tissue culture systems with which to study chronic brain disease. Here we investigate whether a 3D bioengineered neural tissue model derived from human induced pluripotent stem cells (hiPSCs) can remain stable and functional for multiple years in culture. Silk-based scaffolds were seeded with neurons and glial cells derived from hiPSCs supplied by human donors who were either healthy or had been diagnosed with Alzheimer’s disease. Cell retention and markers of stress remained stable for over 2 years. Diseased samples displayed decreased spontaneous electrical activity and a subset displayed sporadic-like indicators of increased pathological β-amyloid and tau markers characteristic of Alzheimer’s disease with concomitant increases in oxidative stress. We conclude that the long-term stability of the platform is suited to study chronic brain disease including neurodegeneration.