Medical Research: What is the background for this study? What are the main findings?
Dr. Bursac: Researchers have tried for a long time to coax human muscle cells (obtained from needle biopsies) into contracting muscle fibers in a dish in order to be able to study human muscle physiology ex vivo. We are the first group that succeeded by carefully optimizing culture conditions including methods to expand and then culture cells in three-dimensional hydrogel matrices under passive tension. By doing so, we made first human muscle model that in response to electrical stimulation generates classical muscle contractile responses (twitch and tetanus). We have also shown that these engineered muscles (that we call “myobundles”) contract in response to acetylcholine as it naturally happens when neurons in our body activate muscle. We demonstrated reproducibility and robustness of the approach by generating functional myobundles with similar properties from 10 independent donor muscle samples. We further went to show that myobundles have intact signaling characteristic of native muscle and respond to diverse set of drugs as human muscles do in clinics.
Medical Research: What should clinicians and patients take away from your report?
Dr. Bursac: This finally enables researchers in the field to study human muscle physiology and drug responses in a dish rather than only being able to look in biochemical outputs (gene and protein expression). As we can get more than 1,000 myobundles from a single small needle muscle biopsy we now have a platform to study functional (or toxic) effects of multiple drugs on the muscle from the same patient, opening doors to novel drug development studies and design of personalized therapeutics.
Medical Research: What recommendations do you have for future research as a result of this study?
Dr. Bursac: With clinicians from Duke we have started obtaining consented needle biopsies from cohorts of patients with muscle disease. We are generating myobundles from these biopsies and are now working to validate, on a patient-to-patient basis, functional and biochemical responses of our myobundles against the results obtained in clinics. Future research in this field will be geared towards increasing the fidelity of this system and using it for studies of human muscle disease and function. Furthermore, the myobundles can be combined with other human cell culture systems into a single in vitro platform, called “body-on-a-chip”. We hope that such multi-organ human microphysiological systems will be more predictive when compared to use of animals in testing the drug safety and efficacy. They would also allow us to systematically study and increase understanding of whole organ-organ interactions which emerge as very important, but notoriously difficult to study in the intact organism.
Lauran Madden, Mark Juhas, William E Kraus, George A Truskey, Nenad Bursac. Bioengineered human myobundles mimic clinical responses of skeletal muscle to drugs. eLife, 2015; 4 DOI: 10.7554/eLife.04885