Contracting Lab Grown Muscle Simulates Effect of Exercise on Muscles
Author: Duke University
Published: 2015/01/13 - Updated: 2025/01/23
Publication Details: Peer-Reviewed, Reports & Proceedings
Topic: Personalized Medicine - Publications List
Page Content: Synopsis - Introduction - Main - Insights, Updates
Synopsis: This article reports on a groundbreaking achievement by researchers at Duke University, who successfully engineered human skeletal muscle tissue in the laboratory that contracts and responds to stimuli similarly to native muscle. By cultivating myogenic precursor cells within a three-dimensional scaffold, the team produced functional muscle fibers capable of reacting to electrical impulses, biochemical signals, and pharmaceuticals. This advancement holds significant potential for drug testing and disease modeling, offering a platform to assess drug efficacy and safety without endangering patients. Moreover, it paves the way for personalized medicine applications, enabling the creation of patient-specific muscle tissues to determine optimal therapeutic strategies - Disabled World (DW).
Introduction
In a laboratory first, Duke researchers have grown human skeletal muscle that contracts and responds just like native tissue to external stimuli such as electrical pulses, biochemical signals and pharmaceuticals.
Focus
The lab-grown tissue should soon allow researchers to test new drugs and study diseases in functioning human muscle outside of the human body.
The study was led by Nenad Bursac, associate professor of biomedical engineering at Duke University, and Lauran Madden, a postdoctoral researcher in Bursac's laboratory. It appears January 13 in the open-access journal eLife.
"The beauty of this work is that it can serve as a test bed for clinical trials in a dish," said Bursac. "We are working to test drugs' efficacy and safety without jeopardizing a patient's health and also to reproduce the functional and biochemical signals of diseases - especially rare ones and those that make taking muscle biopsies difficult."
Bursac and Madden started with a small sample of human cells that had already progressed beyond stem cells but hadn't yet become muscle tissue. They expanded these "myogenic precursors" by more than a 1000-fold, and then put them into a supportive, 3D scaffolding filled with a nourishing gel that allowed them to form aligned and functioning muscle fibers.
"We have a lot of experience making bio-artificial muscles from animal cells in the laboratory, and it still took us a year of adjusting variables like cell and gel density and optimizing the culture matrix and media to make this work with human muscle cells," said Madden.
Madden subjected the new muscle to a barrage of tests to determine how closely it resembled native tissue inside a human body. She found that the muscles robustly contracted in response to electrical stimuli - a first for human muscle grown in a laboratory. She also showed that the signaling pathways allowing nerves to activate the muscle were intact and functional.
To see if the muscle could be used as a proxy for medical tests, Bursac and Madden studied its response to a variety of drugs, including statins used to lower cholesterol and clenbuterol, a drug known to be used off-label as a performance enhancer for athletes.
The effects of the drugs matched those seen in human patients. The statins had a dose-dependent response, causing abnormal fat accumulation at high concentrations. Clenbuterol showed a narrow beneficial window for increased contraction. Both of these effects have been documented in humans. Clenbuterol does not harm muscle tissue in rodents at those doses, showing the lab-grown muscle was giving a truly human response.
"One of our goals is to use this method to provide personalized medicine to patients," said Bursac. "We can take a biopsy from each patient, grow many new muscles to use as test samples and experiment to see which drugs would work best for each person."
This goal may not be far away; Bursac is already working on a study with clinicians at Duke Medicine - including Dwight Koeberl, associate professor of pediatrics - to try to correlate efficacy of drugs in patients with the effects on lab-grown muscles. Bursac's group is also trying to grow contracting human muscles using induced pluripotent stem cells instead of biopsied cells.
"There are a some diseases, like Duchenne Muscular Dystrophy for example, that make taking muscle biopsies difficult," said Bursac. "If we could grow working, testable muscles from induced pluripotent stem cells, we could take one skin or blood sample and never have to bother the patient again."
About the Study Report
Other investigators involved in this study include George Truskey, the R. Eugene and Susie E. Goodson Professor of Biomedical Engineering and senior associate dean for research for the Pratt School of Engineering, and William Krauss, professor of biomedical engineering, medicine and nursing at Duke University.
The research was supported by NIH Grants R01AR055226 and R01AR065873 from the National Institute of Arthritis and Musculoskeletal and Skin Disease and UH2TR000505 from the NIH Common Fund for the Micro-physiological Systems Initiative.
"Bio-engineered human myobundles mimic clinical responses of skeletal muscle to drugs," Lauran Madden, Mark Juhas, William E Kraus, George A Truskey, Nenad Bursac. eLife, Jan. 13, 2015.
Insights, Analysis, and Developments
Editorial Note:The exploration of muscle-related conditions like polyarthralgia, myalgia, and muscular dystrophies highlights the critical intersection of medical science and patient care. As we advance in understanding these disorders through research and clinical practice, it becomes increasingly clear that personalized treatment plans, informed by the latest in genetic and physiological research, are essential. The journey from symptom management to potentially curative therapies involves a complex interplay of medical innovation, patient education, and advocacy. This article underscores the importance of continued research into muscle health, not only to alleviate current suffering but to prevent future instances of these debilitating conditions. It's a call to action for both the medical community and society to support those affected by muscle disorders, ensuring that advancements in treatment and care are accessible to all, thus fostering a future where individuals with muscle conditions can lead fuller, more active lives
- Disabled World (DW).Attribution/Source(s): This peer reviewed publication was selected for publishing by the editors of Disabled World (DW) due to its relevance to the disability community. Originally authored by Duke University and published on 2015/01/13, this content may have been edited for style, clarity, or brevity. For further details or clarifications, Duke University can be contacted at duke.edu NOTE: Disabled World does not provide any warranties or endorsements related to this article.