Stem Cell Transplantation for Degenerative Muscle Diseases

  • Berkcan Akpinar
  • Elizabeth C. Stahl
  • Aiping Lu
  • Johnny HuardEmail author
Part of the Stem Cell Biology and Regenerative Medicine book series (STEMCELL)


Under normal physiological conditions, skeletal muscle has a robust potential for tissue regeneration, which requires the activation of muscle progenitor cells (MPCs). However, degenerative muscle disease triggers recurrent muscle fiber destruction and repair, requiring persistent activation of MPCs, and ultimately leading to depletion of the progenitor cell pool. Duchenne muscular dystrophy (DMD) is a classic example of degenerative muscle disease which results in a reduced and dysfunctional progenitor cell pool, a phenomenon known as MPC depletion. Although DMD is a congenital disease, patients do not exhibit symptoms until 3–5 years of age, which coincides with MPC depletion. Replenishment of the MPC pool through cell therapy has therefore been explored as a potential treatment for DMD and other related degenerative muscle diseases. Several preclinical and clinical studies are ongoing to evaluate the efficacy of stem cell transplantation in patients with DMD. Notably, these studies are investigating various cell sources, genetic manipulations, and administration routes to achieve optimal treatment. In the past, studies have been hindered by cell availability, poor engraftment, and limited myogenic differentiation ability. Recent findings have revealed the many complexities of the degenerative muscle microenvironment, which include chronic inflammation, ectopic ossification, fatty infiltration, and pathological fibrosis. This hostile environment likely influences progenitor cell survival, engraftment, and differentiation after stem cell transplantation. This chapter aims to describe several clinical and preclinical examples of cell transplantation, highlighting the advantages and disadvantages of various approaches, while emphasizing the importance of the cellular and molecular disease environment in order to afford successful cell therapy.


Muscle progenitor cell Stem cell transplantation Duchenne muscular dystrophy Stem cell depletion Gene therapy 

List of Abbreviations


Aorta-derived mesoangioblast


Dystrophin-glycoprotein complex


Double-knockout (dystrophin/utrophin)


Duchenne muscular dystrophy


Extracellular matrix


Embryonic stem cell


Fluorescence-activated cell sorting


Fibro-adipogenic progenitor cell


Fibroblast growth factor


Growth differentiation factor


Golden retriever muscular dystrophy


Hepatocyte growth factor


Human leukocyte antigen


Heterotopic ossification




Insulin growth factor


Integrin-linked kinase


Intramyocellular lipid accumulation


Induced pluripotent stem cell


Mitogen-activating protein kinase


Muscle-derived stem cell


Myoendothelial cell


Matrix metalloproteinase


Muscle progenitor cell


Mesenchymal stem cell


Nuclear factor kappa B


Nitric oxide


Calcium release-activated calcium channel protein 1


Paired box 7


Pericyte-derived progenitor cell


Reactive oxygen species




Stress urinary incontinence


Transforming growth factor


Tissue inhibitor of metalloproteinase


Vascular endothelial growth factor


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Copyright information

© Springer Science+Business Media New York 2016

Authors and Affiliations

  • Berkcan Akpinar
    • 1
  • Elizabeth C. Stahl
    • 1
  • Aiping Lu
    • 1
  • Johnny Huard
    • 1
    Email author
  1. 1.Department of Orthopaedic SurgeryUniversity of Pittsburgh School of MedicinePittsburghUSA

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