Open AccessFunctional and Sustainable 3D Human Neural Network Models from Pluripotent Stem Cells
Author(s) -
William Cantley,
Chuang Du,
Selene Lomoio,
Thomas DePalma,
Emily Peirent,
Dominic Kleinknecht,
Martin Hunter,
Min D. Tang-Schomer,
Giuseppina Tesco,
David L. Kaplan
Publication year - 2018
Publication title -
acs biomaterials science and engineering
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.082
H-Index - 50
ISSN - 2373-9878
DOI - 10.1021/acsbiomaterials.8b00622
Subject(s) - induced pluripotent stem cell , neuroscience , biology , neural stem cell , embryoid body , neural development , stem cell , embryonic stem cell , microbiology and biotechnology , gene , genetics
Three-dimensional in vitro cell culture models, particularly for the central nervous system, allow for the exploration of mechanisms of organ development, cellular interactions, and disease progression within defined environments. Here we describe the development and characterization of three-dimensional tissue models that promote the differentiation and long-term survival of functional neural networks. These tissue cultures show diverse cell populations including neurons and glial cells (astrocytes) interacting in 3D with spontaneous neural activity confirmed through electrophysiological recordings and calcium imaging over at least 8 months. This approach 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. This tissue model has been tested in stem cells derived from healthy individuals as well as Alzheimer's and Parkinson's disease patients, with similar growth and gene expression responses indicating potential use in the modeling of disease states related to neurodegenerative diseases.