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New Method to Grow and Transplant Muscle Stem Cells Holds Promise for Treatment of Muscular Dystrophy

Results reported in the Journal of Neuromuscular Diseases

June 28, 2016
Satellite cells are stem cells found in skeletal muscles. While transplantation of such muscle stem cells can be a potent therapy for degenerative muscle diseases such as Duchenne muscular dystrophy, these cells tend to lose their transplantation efficiency when cultured in vitro. In a study in the current issue of the Journal of Neuromuscular Diseases, researchers treated these stem cells with leukemia inhibitory factor (LIF), which effectively maintained the undifferentiated state of the satellite cells and enhanced their transplantation efficiency.

To have enough cells for transplantation, they must be grown in vitro and prevented from differentiating before transplantation. Several growth factors, cytokines, and chemicals have been used in muscle stem cell cultures, but the optimal culture conditions required to maintain the undifferentiated state, inhibit differentiation, and enhance eventual transplantation efficiency have not yet been established.

LIF is thought to be involved in muscle regeneration. The investigators found that when LIF-treated muscle stem cells were transplanted to skeletal muscle, they formed two to three times more muscle fibers as control cells did.

“To the best of our knowledge, this study provides the first report of the effect of LIF on the transplantation efficiency of primary satellite cells,” explained Shin’ichi Takeda, MD, PhD, of the Department of Molecular Therapy, National Institute of Neuroscience, National Center of Neurology and Psychiatry, Kodaira, Japan. “This research enables us to get one step closer to the optimal culture conditions for muscle stem cells.”

Caption: Representative immunohistochemistry of GFP-positive fibers in transplanted muscles at 2 weeks after transplantation. Newly grown muscle fibers formed by transplanted cells appear in green. The amount of fibers in the LIF-treated muscles is much greater than in the untreated (vehicle) muscles. Low-power field images were shown in left and center. Scale bar: 300 µm. High-power field image was shown in right. Scale bar: 100 µm.

Dr. Takeda added, “However, precise mechanisms of LIF for the enhancement of transplantation efficiency remain unknown. Investigations aimed at determining the downstream targets of LIF would help to clarify the functional importance of LIF in muscle regeneration, and further its potential application in cell transplantation therapy.”

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NOTES FOR EDITORS

“Enhancement of Satellite Cell Transplantation Efficiency by Leukemia Inhibitory Factor,” by N. Ito, N. Shimizu, H. Tanaka and S. Takeda (DOI: 10.3233/JND-160156), published in the Journal of Neuromuscular Diseases, Volume 3, Issue 2 (June 2016) by IOS Press. The study is openly available at http://content.iospress.com/articles/journal-of-neuromuscular-diseases/jnd160156.

Contact Daphne Watrin, IOS Press, +31 20 688 3355, d.watrin@iospress.nl for additional information. Journalists who wish to interview the authors should contact Shin’ichi Takeda, MD, PhD, at takeda@ncnp.go.jp.

ABOUT THE JOURNAL OF NEUROMUSCULAR DISEASES (JND)

Launched in June 2014, the Journal of Neuromuscular Diseases facilitates progress in understanding the molecular genetics/correlates, pathogenesis, pharmacology, diagnosis and treatment of acquired and genetic neuromuscular diseases (including muscular dystrophy, myasthenia gravis, spinal muscular atrophy, neuropathies, myopathies, myotonias and myositis). The journal publishes research reports, reviews, short communications. Guided by Editors-in-Chief Carsten G. Bönnemann (National Institute of Neurological Disorders and Stroke, NIH) and Hanns Lochmüller (Institute of Genetic Medicine, Newcastle University), the journal is dedicated to providing an open forum for original research in basic science, translational and clinical research that will improve our fundamental understanding and lead to effective treatments of neuromuscular diseases.

ABOUT IOS PRESS

Commencing its publishing activities in 1987, IOS Press is headquartered in Amsterdam with satellite offices in the USA, Germany, India and China and serves the information needs of scientific and medical communities worldwide. IOS Press now publishes over 100 international journals and about 75 book titles each year on subjects ranging from computer sciences and mathematics to medicine and the natural sciences.