Cell Therapy of α-Sarcoglycan Null Dystrophic Mice Through Intra-Arterial Delivery of Mesoangioblasts

Abstract

Preclinical or clinical trials for muscular dystrophies have met with modest success, mainly because of inefficient delivery of viral vectors or donor cells to dystrophic muscles. We report here that intra-arterial delivery of wild-type mesoangioblasts, a class of vessel-associated stem cells, corrects morphologically and functionally the dystrophic phenotype of virtually all downstream muscles in adult immunocompetent alpha-sarcoglycan (alpha-SG) null mice, a model organism for limb-girdle muscular dystrophy. When mesoangioblasts isolated from juvenile dystrophic mice and transduced with a lentiviral vector expressing alpha-SG were injected into the femoral artery of dystrophic mice, they reconstituted skeletal muscle in a manner similar to that seen in wild-type cells. The success of this protocol was mainly due to widespread distribution of donor stem cells through the capillary network, a distinct advantage of this strategy over previous approaches.

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.…”

Engraftment of mesenchymal stem cells into dystrophin-deficient mice is not accompanied by functional recovery

“…Encouraging results have been obtained following the transplantation of several stem cell preparations [29,[41][42][43][44][45][46][47][48] into mouse models of muscular dystrophy. Although most of these studies comprise cell populations isolated directly from muscle tissues, such as satellite cells and mesoangioblasts, stromal cells from bone marrow [29] and adipose tissues [46,47] have also been attributed with in vivo muscle regenerative potential.…”