To date several organs like liver, lung, heart and others have been grown/cultured artificially in a laboratory that can recapitulate the morphology and functionality of the naturally existing organs. These organs were also transplanted in to humans that could successfully recapitulate the real or native organs. However there has not been much success with the muscle. Cell cultures and human biopsies are in use to study the role, progression and effects of muscle diseases. Various drugs, targeting myopathies were also tested on these models in-vitro for understanding the efficacy and side effects on the muscle although these models do not recapitulate the native muscle in organization and function.
In the light of these facts, a latest study led by Nenad Bursac, associate professor of biomedical engineering at Duke University, and Lauran Madden, a postdoctoral researcher in Bursac’s laboratory answered the need for a clinical model that recapitulates native muscle. The laboratory engineered muscle showed the properties like aligned architecture, multinucleated and striated myofibers, Pax7+ cell pool (satellite cells) and contractile nature as in the native muscle. Researchers have designed a biomimetic human skeletal muscle culture system (“myobundle”) that shows contractile functions and responses to a wide range of stimuli. The myobundles were engineered using a hydrogel molding technique. Briefly, the muscle precursor cells cultured from human muscle biopsies were allowed to fuse by compaction in a mold using a hydrogel mixture containing matrigel, thrombin, fibrinogen and media for 3 to 5 days. Then these compacted cells were allowed to align and differentiate in low serum media to look like a tiny muscle or myobundle. After a few days in culture, these myobundles started to exhibit the properties of twitching and contractile responses to electric stimuli. These structures were further tested for the molecular markers exhibited by the native muscle. The utility of these myobundles for preclinical drug testing was studied by analyzing the responses to drugs like statins used to lower cholesterol and clenbuterol, a drug known to be used off-label as a performance enhancer for athletes. These engineered myobundles responded the same way as in human patients, supporting their worth for the preclinical studies.
“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.” Bursac’s group is working towards the development of these myobundles from induced pluripotent stem cells instead of cells from human biopsies. “There are 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.” This study is published in eLife open access journal on 13th of January 2015.
For more information: http://elifesciences.org/content/early/2015/01/09/eLife.04885
Disclaimer: This article does not reflect any personal views of the authors/editors