You are hereAugust 6, 2018 | ESCs/iPSCs
Organ-on-Chip Stem Cell Coculture Provides Boost for Study of Motor Neuron Disease
Review of “Human iPSC-Derived Endothelial Cells and Micro-engineered Organ-Chip Enhance Neuronal Development” from Stem Cell Reports by Stuart P. Atkinson
In vitro testing of induced pluripotent stem cell (iPSC)-derived cell types suffers from a number of limitations, including a lack of functional maturity in resulting cells . Researchers from the laboratories of Samuel Sances and Clive N. Svendsen (Cedars-Sinai Medical Center, Los Angeles, CA, USA) sought to develop an in vitro culture system that enhances the maturation and function of iPSC-derived spinal motor neurons (spMNs) by generating an iPSC-based culture system that better recapitulates the in vivo three-dimensional (3D) microenvironment. The team hopes that fully functional iPSC-derived spMNs may represent an exciting treatment option for disorders such as amyotrophic lateral sclerosis (ALS).
Their new study assessed the potential for 3D organ-on-chip micro-engineered cocultures of differentiating spinal neural progenitor cells (iPSC-derived spNPCs) with brain microvascular endothelial cells (iPSC-derived BMECs) [2, 3] as a possible means to create an appropriate microenvironment to induce spMN differentiation and maturation . Excitingly, analysis of this organ-on-chip system suggested an increase in spMN activity and the generation of an in vivo-like gene expression profile, promoting this model system as a highly useful tool in the fight against motor neuron-related diseases.
The authors found coculture on the organ-on-chip culture promoted vascular-neural interactions between the iPSC-derived vasculature (BMECs) and iPSC-derived neural tissue (differentiating spNPCs), affecting both neural development and neuron-vasculature pathways, and culminating in the enhancement of both differentiating spMN function and signaling. Importantly, organ-on-chip coculture induced maturation to a greater extent than co-culture in 96-well plates, as exemplified by increased calcium transient function and the elevated transcription of in vivo spinal cord developmental genes.
The authors hope that longer-term cultures may further enhance maturity of spMNs and note the suitability of the organ-on-chip culture for controlled administration of prospective therapeutics and the study of human blood-spinal cord barrier penetrance, neural activity modulation, and neural disease mechanisms.
For more on how organ-on-chip culture may propel iPSC-derived cells towards maturity and the clinic, stay tuned to the Stem Cells Portal!
- Avior Y, Sagi I, and Benvenisty N, Pluripotent stem cells in disease modelling and drug discovery. Nature Reviews Molecular Cell Biology 2016;17:170.
- Palmer TD, Willhoite AR, and Gage FH, Vascular niche for adult hippocampal neurogenesis. Journal of Comparative Neurology 2000;425:479-494.
- Shen Q, Goderie SK, Jin L, et al., Endothelial Cells Stimulate Self-Renewal and Expand Neurogenesis of Neural Stem Cells. Science 2004;304:1338-1340.
- Sances S, Ho R, Vatine G, et al., Human iPSC-Derived Endothelial Cells and Microengineered Organ-Chip Enhance Neuronal Development. Stem Cell Reports 2018;10:1222-1236.