Stem Cells Used to Grow Neuromuscular Junctions

The systems are models that reconstruct how organs or a series of organs function in the body. Their use could fast-track medical research and drug testing, potentially delivering life-saving breakthroughs much more rapidly than the typical 10-year trajectory most drugs take now to get through animal and patient trials.

“These types of systems have to be developed if you ever want to get to a human-on-a-chip that recreates human function,” said Dr. James Hickman, a UCF bioengineer who led the groundbreaking research. “It’s taken many trials over a number of years to get this to occur using human derived stem cells."

Dr. Hickman’s study, funded through the US National Institute of Neurological Disorders and Stroke (NINDS) at the National Institutes of Health (Bethesda, MD, USA), was published in the December 2011 issue of the journal Biomaterials. Dr. Hickman is enthusiastic about the future of his research because several federal agencies recently launched an ambitious plan to jump-start research in human-on-a-chip models by making available at least USD 140 million in grant funding.

The goal of the call for action is to generate systems that include various miniature organs connected in lifelike ways to simulate human body function. This would make it possible, for instance, to evaluate drugs on human cells well before they could be tested safely and ethically on living humans. The technique could potentially be more effective than testing in lab mice and other animals currently used to screen potential drug candidates and to develop other medical treatments.

Such traditional animal testing is not only slow and expensive, but frequently leads to failures that might be overcome with better testing options. The limitations of conventional testing alternatives have dramatically slowed the emergence of new drugs, according to Dr. Hickman.

The successful UCF technique began with a collaborator, Brown University (Providence, RI, USA) Prof. Herman Vandenburgh, who gathered muscle stem cells via biopsy from adult volunteers.

Dr. Nadine Guo, a UCF research professor, conducted a series of experiments and found that numerous conditions had to come together just right to make the muscle and spinal cord cells “happy” enough to join and form working junctions. This meant searching different concentrations of cells and various timescales, among other parameters, before hitting on the suitable conditions. “Right now we rely a lot on animal systems for medical research but this is a pure human system,” Dr. Guo concluded. “This work proved that, biologically, this is workable.”

In addition to being a key requirement for any complete human-on-a-chip model, such nerve-muscle junctions might themselves prove important research tools. These junctions play key roles in amyotrophic lateral sclerosis, also known as Lou Gehrig’s disease, in spinal cord injury, and in other debilitating or life-threatening disorders. With further development, the researchers’ methods could be used to test new drugs or other treatments for these disorders even before more expansive chip-based models are developed.

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