Mesoangioblast stem cells ameliorate muscle function in dystrophic dogs

Abstract

Duchenne muscular dystrophy remains an untreatable genetic disease that severely limits motility and life expectancy in affected children. The only animal model specifically reproducing the alterations in the dystrophin gene and the full spectrum of human pathology is the golden retriever dog model. Affected animals present a single mutation in intron 6, resulting in complete absence of the dystrophin protein, and early and severe muscle degeneration with nearly complete loss of motility and walking ability. Death usually occurs at about 1 year of age as a result of failure of respiratory muscles. Here we report that intra-arterial delivery of wild-type canine mesoangioblasts (vessel-associated stem cells) results in an extensive recovery of dystrophin expression, normal muscle morphology and function (confirmed by measurement of contraction force on single fibres). The outcome is a remarkable clinical amelioration and preservation of active motility. These data qualify mesoangioblasts as candidates for future stem cell therapy for Duchenne patients.

Systemic Delivery of Allogenic Muscle Stem Cells Induces Long-Term Muscle Repair and Clinical Efficacy in Duchenne Muscular Dystrophy Dogs

“…62 In return, whether MDSC are able to have tissue and clinical impact on a clinically relevant animal model has not been investigated, except for the mesoangioblasts. 33 Here, we report the reproducible isolation based on delayed adhesion properties of canine MDSC that we named MuStem cells, and demonstrate for the first time that the systemic delivery of these cells in dystrophic dogs allows dystrophin recovery, efficiently prevents muscle deterioration, and contributes to a global and persistent stabilization of the dog's clinical status.…”

“…31 Wild-type mesoangioblast transplantation corrected the muscle dystrophic phenotype in ␣-sarcoglycan null mice, 32 and even mobility in the golden retriever muscular dystrophy (GRMD) dogs. 33 MDSCs were isolated from mouse muscle, taking advantage of their delayed propensity to adhere on collagen-coated surfaces. 30,34 When compared to myoblasts, these cells exhibited an improved ability to restore dystrophin ϩ fibers following injection in mdx muscles.…”

Pericytes resident in postnatal skeletal muscle differentiate into muscle fibres and generate satellite cells

“…Nevertheless, in the last ten years, evidence has accumulated that other progenitors can contribute to skeletal muscle regeneration either by direct fusion or by entering the satellite cell pool [6][7][8][27][28][29][30][31][32][33][34][35][36] . When identified, the anatomical niche of these cells has been often associated with blood vessels (endothelial cells, pericytes and also haematopoietic cells).…”

Adiponectin as a tissue regenerating hormone: more than a metabolic function

“…Mesoangioblasts, multipotent progenitors of mesodermal tissues, particularly attracted scientific attention for their possible use in stem cell therapy since they ameliorated some myopathies in animal models. For example, intra-arterial delivery of mesoangioblasts corrects morphology and function of muscles in sarcoglycan-null mice (Sgca-null) and dystrophic dogs, where it induces extensive recovery of normal dystrophin expression [48,[57][58][59]. In addition to the successful role on satellite cells, recent results highlight that gAd positively affects mesoangioblast features.…”