PlGF-MMP-9-expressing cells restore microcirculation and efficacy of cell therapy in aged dystrophic muscle.
Sclerosis and reduced microvessel density characterize advanced stages of muscular dystrophy and hamper cell or gene delivery, precluding treatment of most individuals with Duchenne muscular dystrophy. Modified tendon fibroblasts expressing an angiogenic factor (placenta growth factor, PlGF) and a metalloproteinase (matrix metalloproteinase-9, MMP-9) are able to restore a vascular network and reduce collagen deposition, allowing efficient cell therapy in aged dystrophic mice. These data open the possibility of extending new therapies to currently untreatable individuals.
Gargioli
Cesare
C
San Raffaele Biomedical Park Foundation of Rome, 100 Via Castel Romano, 10028 Rome, Italy.
Coletta
Marcello
M
De Grandis
Fabrizio
F
Cannata
Stefano M
SM
Cossu
Giulio
G
D000818:Animals; D015153:Blotting, Western; D064987:Cell- and Tissue-Based Therapy / Q000379:methods*; D003094:Collagen / Q000378:metabolism; D005347:Fibroblasts / Q000378:metabolism; D005455:Fluorescent Antibody Technique; D006909:Hydroxyproline / Q000032:analysis; D007150:Immunohistochemistry; D020780:Matrix Metalloproteinase 9 / Q000378:metabolism*; D051379:Mice; D008810:Mice, Inbred C57BL; D018482:Muscle, Skeletal / Q000098:blood supply* / Q000378:metabolism; D020388:Muscular Dystrophy, Duchenne / Q000628:therapy*; D000072483:Placenta Growth Factor; D011257:Pregnancy Proteins / Q000378:metabolism*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D049031:Sarcoglycans / Q000172:deficiency; D013710:Tendons / Q000166:cytology
C000608037:Pgf protein, mouse; D011257:Pregnancy Proteins; D049031:Sarcoglycans; D000072483:Placenta Growth Factor; D003094:Collagen; D020780:Matrix Metalloproteinase 9; D006909:Hydroxyproline