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Stem Cell Transplantation for Degenerative Muscle Diseases

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

Abstract

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.

Keywords

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

List of Abbreviations

ADM

Aorta-derived mesoangioblast

DGC

Dystrophin-glycoprotein complex

DKO

Double-knockout (dystrophin/utrophin)

DMD

Duchenne muscular dystrophy

ECM

Extracellular matrix

ESC

Embryonic stem cell

FACS

Fluorescence-activated cell sorting

FAP

Fibro-adipogenic progenitor cell

FGF

Fibroblast growth factor

GDF

Growth differentiation factor

GRMD

Golden retriever muscular dystrophy

HGF

Hepatocyte growth factor

HLA

Human leukocyte antigen

HO

Heterotopic ossification

IA

Intra-arterial

IGF

Insulin growth factor

ILK

Integrin-linked kinase

IMCL

Intramyocellular lipid accumulation

iPSC

Induced pluripotent stem cell

MAPK

Mitogen-activating protein kinase

MDSC

Muscle-derived stem cell

MEC

Myoendothelial cell

MMP

Matrix metalloproteinase

MPC

Muscle progenitor cell

MSC

Mesenchymal stem cell

NF-kB

Nuclear factor kappa B

NO

Nitric oxide

ORAI-1

Calcium release-activated calcium channel protein 1

PAX7

Paired box 7

PDPC

Pericyte-derived progenitor cell

ROS

Reactive oxygen species

SCGA

Alpha-sarcoglycan

SUI

Stress urinary incontinence

TGF

Transforming growth factor

TIMP

Tissue inhibitor of metalloproteinase

VEGF

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
  1. 1.Department of Orthopaedic SurgeryUniversity of Pittsburgh School of MedicinePittsburghUSA

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