Human Spinal Organoid-on-a-Chip to Model Nociceptive Circuitry for Pain Therapeutics Discovery

Zheng Ao, Hongwei Cai, Zhuhao Wu, Jonathan Krzesniak, Chunhui Tian, Yvonne Y. Lai, Ken Mackie, Feng Guo

Research output: Contribution to journalArticlepeer-review

33 Scopus citations

Abstract

The discovery of new pain therapeutics targeting human nociceptive circuitry is an emerging, exciting, and rewarding field. However, current models for evaluating prospective new therapeutics [e.g., animals and two-dimensional (2D) in vitro cultures] fail to fully recapitulate the complexity of human nociceptive neuron and dorsal horn neuron biology, significantly limiting the development of novel pain therapeutics. Here, we report human spinal organoid-on-a-chip devices for modeling the biology and electrophysiology of human nociceptive neurons and dorsal horn interneurons in nociceptive circuitry. Our device can be simply made through the integration of a membrane with a three-dimensional (3D)-printed organoid holder. By combining air–liquid interface culture and spinal organoid protocols, our devices can differentiate human stem cells into human sensori-spinal-cord organoids with dorsal spinal cord interneurons and sensory neurons. By easily transferring from culture well plates to the multiple-electrode array (MEA) system, our device also allows the plug-and-play measurement of organoid activity for testing nociceptive modulators (e.g., mustard oil, capsaicin, velvet ant venom, etc.). Our organoid-on-a-chip devices are cost-efficient, scalable, easy to use, and compatible with conventional well plates, allowing the plug-and-play measurement of spinal organoid electrophysiology. By the integration of human sensory-spinal-cord organoids with our organoid-on-a-chip devices, our method may hold the promising potential to screen and validate novel therapeutics for human pain medicine discovery.

Original languageEnglish
Pages (from-to)1365-1372
Number of pages8
JournalAnalytical Chemistry
Volume94
Issue number2
DOIs
StatePublished - 18 Jan 2022
Externally publishedYes

Fingerprint

Dive into the research topics of 'Human Spinal Organoid-on-a-Chip to Model Nociceptive Circuitry for Pain Therapeutics Discovery'. Together they form a unique fingerprint.

Cite this