University of Central
Florida (UCF) researchers, for the first time, have used stem cells to
grow neuromuscular junctions between human muscle cells and human spinal cord
cells, the key connectors used by the brain to communicate and control muscles
in the body.
The success at UCF is a critical step
in developing “human-on-a-chip” systems. The systems are models that recreate
how organs or a series of organs function in the body. Their use could
accelerate medical research and drug testing, potentially delivering
life-saving breakthroughs much more quickly than the typical ten-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,”
says James Hickman, a UCF bioengineer who led the breakthrough research. “It’s
taken many trials over a number of years to get this to occur using human
derived stem cells.”
Hickman’s work, funded through the
National Institute of Neurological Disorders and Stroke (NINDS) at the National
Institutes of Health, is described in Biomaterials.
Hickman is excited 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 $140 million in grant funding.
The National Institutes of Health
(NIH), the Defense Advanced Research Projects Agency (DARPA), and the Federal
Drug Administration (FDA) are leading the research push.
The goal of the call for action is to
produce systems that include various miniature organs connected in realistic
ways to simulate human body function. This would make it possible, for
instance, to test drugs on human cells well before they could safely and
ethically be tested on living humans. The technique could potentially be more
effective than testing in mice and other animals currently used to screen
promising drug candidates and to develop other medical treatments.
Such conventional animal testing is
not only slow and expensive, but often leads to failures that might be overcome
with better testing options. The limitations of conventional testing options
have dramatically slowed the emergence of new drugs, Hickman says.
The successful UCF technique began
with a collaborator, Brown University Professor Emeritus Herman Vandenburgh,
who collected muscle stem cells via biopsy from adult volunteers. Stem cells
are cells that can, under the right conditions, grow into specific forms. They
can be found among normal cells in adults, as well as in developing fetuses.
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 exploring different
concentrations of cells and various timescales, among other parameters, before
hitting on the right conditions.
“Right now we rely a lot on animal
systems for medical research but this is a pure human system,” Guo says. “This
work proved that, biologically, this is workable.”
Besides 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, commonly known as Lou Gehrig’s disease, in
spinal cord injury, and in other debilitating or life threatening conditions. With
further development, the team’s techniques could be used to test new drugs or
other treatments for these conditions even before more expansive chip-based
models are developed.