Development of a Three Dimensional Bioengineered hiPSC Derived Neural Network Model for the Study of Neurological Diseases
Abstract: Three-dimensional (3D) in vitro cell culture models, particularly
for the central nervous system, allow unparalleled exploration of human organ development,
cellular interactions, and disease progression within defined environments. Here we
describe the development and characterization of 3D tissue models that promote the
differentiation and long-term survival of functional neural ne... read moretworks. These tissue models
show diverse cell populations, including neurons and astroglial cells, interacting
three-dimensionally with spontaneous neural activity. Electrophysiological recordings and
calcium imaging performed over at least 14 months confirms this activity. This model allows
for the direct integration of pluripotent stem cells into the 3D construct bypassing early
neural differentiation steps (embryoid bodies and neural rosettes), which streamlines the
process while also providing a system that can be manipulated to support a variety of
experimental applications. We have tested this tissue model with stem cells derived from
healthy individuals as well as from Alzheimer's and Parkinson's disease patients. Similar
growth and gene expression indicate potential use in the modeling of disease states related
Thesis (Ph.D.)--Tufts University, 2018.
Submitted to the Dept. of Cell, Molecular & Developmental Biology.
Advisors: David Kaplan, and Yongie Yang.
Committee: James Schwob, and Lauren Black.
Keywords: Biomedical engineering, Cellular biology, and Neurosciences.read less