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Updated: May 9, 2026
Purification and Transplantation of Myogenic Progenitor Cell Derived Exosomes to Improve Cardiac Function in Duchenne Muscular Dystrophic Mice
Published on: April 10, 2019
Reducing CTGF/CCN2 slows down mdx muscle dystrophy and improves cell therapy
Maria Gabriela Morales1, Jaime Gutierrez, Claudio Cabello-Verrugio
1Laboratorio de Diferenciación Celular y Patología, Centro de Regulación Celular y Patología (CRCP), Centro de Regeneración y Envejecimiento (CARE), Departamento de Biología Celular y Molecular, Facultad de Ciencias Biológicas, Pontificia Universidad Católica de Chile, Santiago, Chile.
Abstract:
In Duchenne muscular dystrophy (DMD) and the mdx mouse model, the absence of the cytoskeletal protein dystrophin causes defective anchoring of myofibres to the basal lamina. The resultant myofibre degeneration and necrosis lead to a progressive loss of muscle mass, increased fibrosis and ultimately fatal weakness. Connective tissue growth factor (CTGF/CCN-2) is critically involved in several chronic fibro-degenerative diseases. In DMD, the role of CTGF might extend well beyond replacement fibrosis secondary to loss of muscle fibres, since its overexpression in skeletal muscle could by itself induce a dystrophic phenotype. Using two independent approaches, we here show that mdx mice with reduced CTGF availability do indeed have less severe muscular dystrophy. Mdx mice with hemizygous CTGF deletion (mdx-Ctgf+/-), and mdx mice treated with a neutralizing anti-CTGF monoclonal antibody (FG-3019), performed better in an exercise endurance test, had better muscle strength in isolated muscles and reduced skeletal muscle impairment, apoptotic damage and fibrosis. Transforming growth factor type-β (TGF-β), pERK1/2 and p38 signalling remained unaffected during CTGF suppression. Moreover, both mdx-Ctgf+/- and FG-3019 treated mdx mice had improved grafting upon intramuscular injection of dystrophin-positive satellite cells. These findings reveal the potential of targeting CTGF to reduce disease progression and to improve cell therapy in DMD.
Insights
Reducing connective tissue growth factor (CTGF) significantly lessens the severity of Duchenne muscular dystrophy (DMD) in mdx mice. This approach improves muscle function and enhances cell therapy outcomes for DMD.
Area of Science:
- Biochemistry
- Genetics
- Cell Biology
Background:
- Duchenne muscular dystrophy (DMD) results from a lack of dystrophin, leading to muscle fiber damage, fibrosis, and weakness.
- Connective tissue growth factor (CTGF/CCN-2) is implicated in fibrotic diseases and may contribute to the dystrophic phenotype in DMD.
Purpose of the Study:
- To investigate the therapeutic potential of reducing CTGF availability in the mdx mouse model of DMD.
- To assess the impact of CTGF suppression on disease progression, muscle function, and cell therapy efficacy.
Main Methods:
- Utilized two independent approaches: genetic deletion of one CTGF allele (mdx-Ctgf+/-) and treatment with an anti-CTGF monoclonal antibody (FG-3019).
- Evaluated muscle performance via exercise endurance tests and isolated muscle strength assessments.
- Quantified skeletal muscle impairment, apoptotic damage, and fibrosis.
- Assessed downstream signaling pathways including TGF-β, pERK1/2, and p38.
- Examined the effect of CTGF suppression on the grafting of dystrophin-positive satellite cells.
Main Results:
- Mdx mice with reduced CTGF showed improved exercise endurance and muscle strength.
- Skeletal muscle impairment, apoptosis, and fibrosis were significantly reduced in CTGF-suppressed mdx mice.
- CTGF suppression did not affect TGF-β, pERK1/2, or p38 signaling pathways.
- Grafting of dystrophin-positive satellite cells was improved in mdx mice with reduced CTGF.
Conclusions:
- Reducing CTGF availability ameliorates the dystrophic phenotype in mdx mice.
- Targeting CTGF represents a promising strategy to slow DMD progression.
- CTGF suppression may enhance the effectiveness of cell-based therapies for DMD.
