Abstract

Duchenne muscular dystrophy (DMD) occurs due to genetic mutations that lead to absence or decrease of dystrophin protein generating progressive muscle degeneration. Cell therapy using mesenchymal stem cell (MSC) has been described as a treatment to DMD. In this work, MSC derived from deciduous teeth, called stem cells from human exfoliated deciduous teeth (SHED), were injected in acupoint as an alternative therapy to minimize muscle degeneration in twenty-two mdx mice. The treatment occurred three times with intervals of 21 days, and animals were analyzed four times: seven days prior treatment (T-7); 10 days after first treatment (T10); 10 days after second treatment (T31); and 10 days after third treatment (T52). Animals were evaluated by wire test for estimate strength and blood was collected to perform a creatinine phosphokinase analysis. After euthanasia, cranial tibial muscles were collected and submitted to histological and immunohistochemistry analyses. Treated groups presented improvement of strength and reduced creatinine phosphokinase levels. Also, a slight dystrophin increase was observed in tibial cranial muscle when aquapuncture was associated SHED. All therapies have minimized muscle degeneration, but the association of aquapuncture with SHED appears to have better effect, reducing muscle damage, suggesting a therapeutic value.

Highlights

  • Muscular dystrophies are neuromuscular diseases genetically related that compromise progressively skeletal muscles

  • We proposed an alternative method to treat Duchenne muscular dystrophy (DMD) using mdx as a model to test the benefits of acupuncture associated with stem cell therapy, a pioneer work in this field

  • Acupoints were selected bilaterally after an accurate assessment of DMD, associated with the benefits they could bring from Traditional Chinese Medicine

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Summary

Introduction

Muscular dystrophies are neuromuscular diseases genetically related that compromise progressively skeletal muscles. Besides stem cell hypothetically could replace damaged cell, and stem cells are able to perform immunomodulation activities that could balance the progression of muscular dystrophy by anti-inflammatory effect [7, 14, 16,17,18]. Gene therapy has been tested to treat DMD [19,20,21,22] and, recently, a combination of stem cells, using induced pluripotent stem cells (iPSC) from a patient with DMD, and gene therapy, correcting genetically the cells using TALENs or CRISPR, restored dystrophin production in vitro [22]

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