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Organ-on-Chip Stem Cell Coculture Provides Boost for Study of Motor Neuron Disease

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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 [1]. 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 [4]. 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!

References

  1. Avior Y, Sagi I, and Benvenisty N, Pluripotent stem cells in disease modelling and drug discovery. Nature Reviews Molecular Cell Biology 2016;17:170.
  2. Palmer TD, Willhoite AR, and Gage FH, Vascular niche for adult hippocampal neurogenesis. Journal of Comparative Neurology 2000;425:479-494.
  3. 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.
  4. 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.