An organ-chip model of sporadic ALS using iPSC-derived spinal cord motor neurons and an integrated blood-brain-like barrier
Summary
Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disorder in which motor neurons (MNs) of the brain and spinal cord degenerate, leading to paralysis. Generating MNs from patient-specific induced pluripotent stem cells (iPSCs) may help elucidate early stages of disease. Here, we combined MNs from patients with early-onset disease with brain microvascular endothelial-like cells in a microfluidic device we termed spinal cord chips (SC-chips) and added media flow, which enhanced neuronal maturation and improved cellular health. Bulk transcriptomic and proteomic analyses of SC-chips revealed differences between control and ALS samples, including increased levels of neurofilaments. Single-nuclei RNA sequencing revealed the presence of two MN subpopulations and an ALS-specific dysregulation of glutamatergic and synaptic signaling. This ALS SC-chip model generates a diversity of mature MNs to better understand ALS pathology in a model that has an active blood-brain barrier-like system for future drug screening. Copyright © 2025 The Author(s). Published by Elsevier Inc. All rights reserved.
| Authors | Lall D, Workman MJ, Sances S, Ondatje BN, Bell S, Lawless G, Woodbury A, West D, Meyer A, Matlock A, Vaibhav V, Van Eyk JE, Svendsen CN |
|---|---|
| Journal | Cell stem cell |
| Publication Date | 2025 Jul 3;32(7):1139-1153.e7 |
| PubMed | 40562033 |
| PubMed Central | PMC12233189 |
| DOI | 10.1016/j.stem.2025.05.015 |