Abstract
BackgroundThe diaphragm is the major respiratory muscle affected by Duchenne muscular dystrophy (DMD) and is responsible for causing 80% of deaths. The use of mechanical forces that act on the body or intermittent pressure on the airways improves the quality of life of patients but does not prevent the progression of respiratory failure. Thus, diseases that require tissue repair, such as DMD, represent a group of pathologies that have great potential for cell therapy. The application of stem cells directly into the diaphragm instead of systemic application can reduce cell migration to other affected areas and increase the chances of muscle reorganisation. The mdx mouse is a suitable animal model for this research because its diaphragmatic phenotype is similar to human DMD. Therefore, the aim of this study was to assess the potential cell implantation in the diaphragm muscle after the xenotransplantation of stem cells.MethodsA total of 9 mice, including 3 control BALB/Cmice, 3 5-month-old mdx mice without stem cell injections and 3 mdx mice injected with stem cells, were used. The animals injected with stem cells underwent laparoscopy so that stem cells from GFP-labelled rabbit olfactory epithelium could be locally injected into the diaphragm muscle. After 8 days, all animals were euthanised, and the diaphragm muscle was dissected and subjected to histological and immunohistochemical analyses.ResultsBoth the fresh diaphragm tissue and immunohistochemical analyses showed immunopositive GFP labelling of some of the cells and immunonegativity of myoblast bundles. In the histological analysis, we observed a reduction in the inflammatory infiltrate as well as the presence of a few peripheral nuclei and myoblast bundles.ConclusionWe were able to implant stem cells into the diaphragm via local injection, which promoted moderate muscle reorganisation. The presence of myoblast bundles cannot be attributed to stem cell incorporation because there was no immunopositive labelling in this structure. It is believed that the formation of the bundles may have been stimulated by cellular signalling mechanisms that have not yet been elucidated.
Highlights
The diaphragm is the major respiratory muscle affected by Duchenne muscular dystrophy (DMD) and is responsible for causing 80% of deaths
At approximately 20 to 30 years of age, depending on the ventilation resources used, the patients die as a result of respiratory muscle impairment, which is the cause of death in 80% of DMD patients, due to respiratory failure in addition to an infection or heart failure
Some basal nuclei can be observed in mdx stem cell treated group (Figure 1, C).The presence of a myoblast bundle is noted only at stem cell treated group and exhibit long and tubular appearance can be observed in low (Figure 1, C) and high magnification (Figure 1, D)
Summary
The diaphragm is the major respiratory muscle affected by Duchenne muscular dystrophy (DMD) and is responsible for causing 80% of deaths. The use of mechanical forces that act on the body or intermittent pressure on the airways improves the quality of life of patients but does not prevent the progression of respiratory failure. Due weakening of respiratory muscle, these patients are unable to generate respiratory pressure (maximal inspiratory pressure and maximal expiratory pressure), and the peak expiratory flow is reduced. All of these factors lead to the premature death of DMD patients [3,7,8]. Negative pressure body ventilators (NPBVs) and bilevel positive airway pressure (BiPAP) improve the quality of life of patients but do not prevent the progression of respiratory failure [6]
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