Scientists Recreate Human Peripheral Nerve Cells’ Interactions on a Chip

Researchers have created the first entirely human small chip that is able to replicate some of the cell-cell interactions occurring in the peripheral human nervous system, according to a recent study.

The Nerve-on-a-Chip platform, developed by AxoSim using organ-on-chip technology, promises to help researchers understand, faster and at lower costs, the human mechanisms of neurodegenerative diseases such as  amyotrophic lateral sclerosis (ALS).

“We developed the Nerve-on-a-Chip technology to give researchers and drug developers a biomimetic model that would provide human data much earlier in the process, thereby saving time and money and allowing researchers to focus on candidates with greater potential,” Michael J. Moore, PhD, said in a press release. Moore is a professor of biomedical engineering at Tulane University and the study’s co-lead author.

“This study confirms the success of our work with our collaborators at AxoSim in creating a powerful tool for human neurology translational and clinical research,” he added.

The study, “Engineering a 3D functional human peripheral nerve in vitro using the Nerve-on-a-Chip platform,” was published in the journal Scientific Reports. 

While animal models have been crucial in understanding several human diseases, the differences in the mechanisms underlying neurodegenerative diseases between animals and humans are the reason why findings of animal studies have not been translated into human therapies.

The complex cellular network and interactions that occur in the human nervous system have been a major roadblock for developing new in vitro (in the lab) human models for researchers to investigate mechanisms of disease, including ALS.

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“Development of organ-on-a-chip systems for neuroscience applications has lagged. Yet there is great need for tools to accelerate the slow pace of new drug R&D [research and development] for neurological disorders,” said Moore.

AxoSim’s Nerve-on-a-Chip platform shows promise in accurately recreating features of the human nervous system. To build it, researchers first generated the building blocks for the platform made of induced pluripotent stem cell (iPSC)-derived neurons and primary human Schwann cells, which are responsible for producing the protective myelin sheath around nerve cells. The cells are then organized into 3D structures, called spheroids, that recreate key cell-cell interactions. (Of note, iPSCs are able to generate almost any type of cell in the body.)

The spheroids are then transferred into the Nerve-on-a-Chip platform where researchers monitor the cells self-organization and whether they mimic the interactions seen in the human nervous system.

Researchers saw that their new model recapitulated numerous aspects of the biology of the peripheral nerves. Specifically, the Nerve-on-a-Chip platform showed a robust axon outgrowth, the process by which the axons grow away from the nerve cell’s body. An axon is a long, slender projection of a neuron whose job is to transmit information (electrical impulses) to different neurons, muscles, and glands.

Moreover, they saw evidence of myelination of the iPSC-derived neurons by the human Schwann cells and were able to perform nerve conduction velocity tests, which measure how fast an electrical impulse moves through nerves.  These tests can identify nerve damage and previously had been possible only in live animals.

“This innovative H [human] NoaC [Nerve-on-a-Chip] platform can be used to create a variety of nerves (motor, sensory, etc.) in the future and has the potential to accelerate the field of human disease modeling, drug discovery, toxicity screening, and precision medicine,” researchers wrote.

“We believe that our Nerve-on-a-Chip platform is the first fully functional biomimetic microphysiological model of myelinated human peripheral nerves. Myelination is critical for proper neuronal functioning and impaired myelination is implicated in many neurological diseases,” said Lowry Curley, PhD, AxoSim’s CEO.

“This new study confirms that our Nerve-on-a-Chip technology can evaluate key electrophysiological [electrical processes in our organism] and histological [tissue] metrics, the gold-standard techniques previously only possible with in vivo and clinical studies,” Curley said.

“We are currently working with a number of major pharmaceutical and biotechnology partners to conduct studies using the platform, and expect this new study will contribute to the growth of our Nerve-on-a-Chip service,” he added.