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Front. Physiol., 08 April 2014 | http://dx.doi.org/10.3389/fphys.2014.00119

Molecular and cell-based therapies for muscle degenerations: a road under construction

  • 1Translational Cardiomyology Laboratory, Department of Development and Reproduction, KUL University of Leuven, Leuven, Belgium
  • 2Interuniversity Institute of Myology, Italy
  • 3Laboratory of Cell Metabolism and Proliferation, Vesalius Research Center, Vlaamse Institute voor Biotechnologie, Leuven, Belgium
  • 4School of Life Sciences, Ecole Polytechnique Fédérale de Lausanne, Lausanne, Switzerland
  • 5Department of Medicine, University of Lausanne Medical School, Lausanne, Switzerland
  • 6Division of Human Anatomy, Department of Public Health, Experimental and Forensic Medicine, University of Pavia, Pavia, Italy

Despite the advances achieved in understanding the molecular biology of muscle cells in the past decades, there is still need for effective treatments of muscular degeneration caused by muscular dystrophies and for counteracting the muscle wasting caused by cachexia or sarcopenia. The corticosteroid medications currently in use for dystrophic patients merely help to control the inflammatory state and only slightly delay the progression of the disease. Unfortunately, walkers and wheel chairs are the only options for such patients to maintain independence and walking capabilities until the respiratory muscles become weak and the mechanical ventilation is needed. On the other hand, myostatin inhibition, IL-6 antagonism and synthetic ghrelin administration are examples of promising treatments in cachexia animal models. In both dystrophies and cachectic syndrome the muscular degeneration is extremely relevant and the translational therapeutic attempts to find a possible cure are well defined. In particular, molecular-based therapies are common options to be explored in order to exploit beneficial treatments for cachexia, while gene/cell therapies are mostly used in the attempt to induce a substantial improvement of the dystrophic muscular phenotype. This review focuses on the description of the use of molecular administrations and gene/stem cell therapy to treat muscular degenerations. It reviews previous trials using cell delivery protocols in mice and patients starting with the use of donor myoblasts, outlining the likely causes for their poor results and briefly focusing on satellite cell studies that raise new hope. Then it proceeds to describe recently identified stem/progenitor cells, including pluripotent stem cells and in relationship to their ability to home within a dystrophic muscle and to differentiate into skeletal muscle cells. Different known features of various stem cells are compared in this perspective, and the few available examples of their use in animal models of muscular degeneration are reported. Since non coding RNAs, including microRNAs (miRNAs), are emerging as prominent players in the regulation of stem cell fates we also provides an outline of the role of microRNAs in the control of myogenic commitment. Finally, based on our current knowledge and the rapid advance in stem cell biology, a prediction of clinical translation for cell therapy protocols combined with molecular treatments is discussed.

Keywords: muscle degeneration, molecular treatments, stem cells, gene and cell therapies, cachexia

Citation: Berardi E, Annibali D, Cassano M, Crippa S and Sampaolesi M (2014) Molecular and cell-based therapies for muscle degenerations: a road under construction. Front. Physiol. 5:119. doi: 10.3389/fphys.2014.00119

Received: 25 November 2013; Accepted: 12 March 2014;
Published online: 08 April 2014.

Edited by:

Carlos Hermano J. Pinheiro, University of São Paulo, Brazil

Reviewed by:

Alessandra Sacco, Sanford-Burnham Medical Research Institute, USA
Radbod Darabi, University of Texas Medical Health Center at Houston, USA

Copyright © 2014 Berardi, Annibali, Cassano, Crippa and Sampaolesi. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

*Correspondence: Maurilio Sampaolesi, Translational Cardiomyology Laboratory, Department of Development and Reproduction, KUL University of Leuven, Stem Cell Research Institute, 49 Herestraat B-3000 Leuven, Belgium e-mail: maurilio.sampaolesi@med.kuleuven.be