An AdventHealth Collaboration Explores the Impact of Microgravity and Electrical Stimulation on Muscle Cell Health in Space

Using a muscle lab-on-chip model aboard the International Space Station (ISS), AdventHealth Translational Research Institute’s Paul M. Coen, PhD, has been working with a multidisciplinary team from the University of Florida and Micro-gRX, Inc., and led by Sibohan Malany, PhD, to examine how microgravity affects muscle cell function. Their latest study found that electrical stimulation (e-stim) applied intermittingly could help reduce gene expression signatures of muscle tissue degradation, paving the way for potential applications in space and on Earth. Titled, “Microgravity Accelerates Skeletal Muscle Degeneration: Functional and Transcriptomic Insights from an ISS Muscle Lab-on-Chip Model," the team’s work was recently published in Stem Cell Reports.

Advancing the Understanding of Muscle Health in a Novel Way
Sarcopenia, the age-related loss of muscle mass, strength and function, increases risk of falls, fractures and injuries and can also contribute to a decline in overall health and quality of life. Mimicking aspects of aging, microgravity accelerates skeletal muscle degeneration, with astronauts experiencing up to a 30% reduction in skeletal muscle mass and strength within just one month of spaceflight.

“Spaceflight and exposure to microgravity provides us with an innovative way to study the mechanisms that are occurring at a cellular level to cause muscle degradation,” shares Dr. Coen. “We aim to take what we learn in space to not only help astronauts but to also develop new interventions that slow muscle loss for older adults here on Earth.”

The team used a Space Tango CubeLab, a specially engineered, shoebox-sized laboratory that was carried to the Space Station aboard SpaceX’s Falcon 9 in partnership with Kennedy Space Center. This miniature lab featured skeletal muscle tissue chips with each chip containing a single 3D bioengineered muscle bundle, also known as a myobundle. Half of the myobundles were engineered from muscle cells obtained from vastus lateralis biopsies from young active adults and the other half from old sedentary participants. An automated system fed nutrients to the myobundles, and electrodes built into each chip allowed the research team to evaluate the response to e-stim-induced muscle contraction. For this specific study, half the cells in each age cohort received intermittent e-stim over a one-week period. A parallel ground study with the same CubeLab hardware was conducted at the University of Florida to serve as the controls.

Findings on the Impacts of Electrical Stimulation on Muscle Cells in Space
This latest study aimed to identify new age-related transcriptional signatures associated with muscle cell exposure to microgravity. Drs. Coen, Malany and the team investigated how microgravity influences myocyte contractile function and gene expression along with any protective effects of e-stim. Key findings included the following:

• Transcriptomic profiling results indicate that the microgravity environment, including launch conditions, did not inhibit myofiber maturation and maintenance during myogenesis, the process of muscle tissue development.
• Younger electrically stimulated myobundles displayed enhanced mitochondrial-related gene expression in microgravity, while older and non-electrically stimulated myobundles were less responsive.
• Comparative analysis between young versus older derived myobundles identified 86 muscle specific age-associated genes altered in microgravity, linked to inflammation, mitochondrial dysfunction and cellular stress.

“Our findings uncovered a unique age-related molecular response in microgravity and supported our hypothesis that electrical stimulation could serve as a potential countermeasure,” says Dr. Coen. “These insights advance our understanding of muscle aging and degeneration and will help guide development of future therapeutic strategies.”

Deeping the Knowledge Base of Muscle Function to Improve Patient Care

Dr. Coen and his research partners at the University of Florida and Micro-gRX, Inc., plan to use the CubeLab platform to further build upon their knowledge base. This includes exploring differences in responses to microgravity and e-stim between male and female muscle cells as well as testing compounds and novel therapeutics that could potentially protect muscle cells from the effects of microgravity.

“Historically, bed rest studies have been used as a model to understand the effects of spaceflight on astronauts,” comments Dr. Coen. “Now, with the CubeLab, we’re flipping the script and using space studies to better understand what is happening to muscles at a cellular level to not only improve the health of astronauts, but also patients on bed rest as well as aging adults in general. This work closely aligns with our current and previous studies on muscle atrophy at the Translational Research Institute.”

To that point, Dr. Coen recently completed and is currently analyzing data from the REST study, which aimed to better understand the role of type 2 diabetes on skeletal muscle atrophy and recovery following bed rest in older adults. Additionally, AdventHealth was recently selected as a clinical site for The Study of Muscle, Mobility and Aging (SOMMA). Funded by the National Institute on Aging (NIA), SOMMA is a prospective, longitudinal cohort study designed to examine the biological properties of skeletal muscle that predict onset of disability or dementia in older adults.

“All these studies – in space and on Earth -- support our greater mission to extend and improve quality of life through world-class, innovative translational research that leads to new discoveries,” concludes Dr. Coen.

Learn more about research conducted at AdventHealth by visiting the AdventHealth Research Institute website.