"Human Muscle" Grown on a Chip... Responses to Nerve Stimulation and High Glucose Confirmed [Reading Science]

KIST Develops Artificial Muscle Model Integrating Muscle, Motor Neurons, and Vascular Endothelial Cells
Tracks Changes in Muscle Function and Metabolism... Potential for Evaluating Drug Candidates and Rehabilitation Treatments

A technology has been developed that integrates the cells that make up human muscles, motor nerves, and blood vessels on a single chip, enabling researchers to examine how muscles change in response to nerve stimulation and a high-glucose environment.

Researchers observed that stimuli similar to those produced by actual exercise activate muscle function, while a high-glucose environment impairs energy metabolism. The technology is expected to advance into a tool for evaluating the effects of drug candidates and rehabilitation treatments using human cells, without relying on animal testing.

Microchip structure and cell culture. Muscle cells are cultured in the chamber at the center of the microchip, while motor neurons cultured in a separate chamber extend axons through microchannels to connect with muscle tissue. The chip is placed in a well plate for culture. Courtesy of the research team.

The Korea Institute of Science and Technology (KIST) announced on Nov. 11 that a research team led by Kim Jihoon, a senior researcher at its Center for Biomolecular Recognition, had jointly developed an artificial muscle model integrating human muscle cells, motor neurons, and vascular endothelial cells on a single microchip with teams led by Professor Son Jangwon of Bucheon St. Mary's Hospital at the Catholic University of Korea and Professor Jung Seok of the Department of Mechanical Engineering at Korea University.

The researchers created three-dimensional muscle tissue from human cells inside the chip and arranged for motor neurons to extend through microchannels and connect to the muscle. They also added vascular endothelial cells, which line the inside of blood vessels, to mimic the environment surrounding muscles in the human body.

While previous studies on muscle chips focused either on replicating muscle tissue itself or on connecting muscles and nerves, this study focused on co-culturing and structurally connecting three types of cells. In particular, the researchers confirmed that a relatively uniform structure could be repeatedly produced through "self-organization," a process in which cells form tissue on their own.

When the researchers repeatedly stimulated the motor neurons formed on the chip, the muscle fibers thickened and muscle contraction responses and activity increased. Genes related to energy metabolism and mitochondrial function were activated, and glucose uptake in response to insulin stimulation also increased. These changes were similar to the functional adaptations seen in muscles during actual exercise.

In contrast, a high-glucose environment impaired energy metabolism and increased reactive oxygen species. However, the experiment did not reproduce the condition of people with diabetes; rather, it modeled metabolic stress caused by high glucose levels.

The researchers also confirmed the role of vascular endothelial cells. When they added these cells to tissue composed of muscle and motor neurons, calcium signaling in the motor neurons was activated, and muscle responses to nerve stimulation improved. The findings show that muscle function is affected not only by muscle cells themselves but also by their interactions with surrounding nerve and vascular cells.

Potential for Evaluating Drugs and Rehabilitation Treatments; Further Validation Needed Before Practical Use

The technology could be used to evaluate the effects on human muscle of potential treatments for sarcopenia, metabolic syndrome, and neuromuscular diseases. It could also be used to compare how stimuli applied during exercise or rehabilitation affect muscle function.

In some cases, drugs that show effects in animal studies produce unexpected responses in humans. Organ-on-a-chip technology, which uses human cells to recreate aspects of the human body's environment, is attracting attention as a new preclinical evaluation tool that could help reduce these discrepancies.

Joint research team. From left: An Jincheol, postdoctoral researcher at the Korea Institute of Science and Technology (KIST); Kim Jihoon, senior researcher at KIST; Professor Son Jangwon of Bucheon St. Mary's Hospital, the Catholic University of Korea; and Professor Jeong Seok of Korea University. Courtesy of KIST.

However, further validation is needed before the technology can be used to evaluate actual drug candidates. The researchers said they need to accumulate data on responses to various stimuli and drugs to determine the range of applications for which the chip can be used, and simplify and automate the chip production and experimental processes. They also cited the inability of organ-on-a-chip technology to reproduce all the complexities of human physiology as a limitation.

"By integrating human muscle cells, motor neurons, and vascular endothelial cells on a single chip, we observed how muscles change in response to nerve stimulation and metabolic conditions," said Kim Jihoon, a senior researcher at KIST. "We will develop this into a preclinical platform for evaluating the effects of potential treatments and rehabilitation stimuli using human cells."

An Jincheol, a postdoctoral researcher at KIST, was the first author of the study. The findings were published in the latest issue of the international journal Advanced Materials.

This content was produced with the assistance of AI translation services.