Author:
Cossu Giulio,Tonlorenzi Rossana,Brunelli Silvia,Sampaolesi Maurilio,Messina Graziella,Azzoni Emanuele,Benedetti Sara,Biressi Stefano,Bonfanti Chiara,Bragg Laricia,Camps Jordi,Cappellari Ornella,Cassano Marco,Ciceri Fabio,Coletta Marcello,Covarello Diego,Crippa Stefania,Cusella-De Angelis M. Gabriella,De Angelis Luciana,Dellavalle Arianna,Diaz-Manera Jordi,Galli Daniela,Galli Francesco,Gargioli Cesare,Gerli Mattia F. M.,Giacomazzi Giorgia,Galvez Beatriz G.,Hoshiya Hidetoshi,Guttinger Maria,Innocenzi Anna,Minasi M. Giulia,Perani Laura,Previtali Stefano C,Quattrocelli Mattia,Ragazzi Martina,Roostalu Urmas,Rossi Giuliana,Scardigli Raffaella,Sirabella Dario,Tedesco Francesco Saverio,Torrente Yvan,Ugarte Gonzalo
Abstract
In 2002 we published an article describing a population of vessel-associated progenitors that we termed mesoangioblasts (MABs). During the past decade evidence had accumulated that during muscle development and regeneration things may be more complex than a simple sequence of binary choices (e.g., dorsal vs. ventral somite). LacZ expressing fibroblasts could fuse with unlabelled myoblasts but not among themselves or with other cell types. Bone marrow derived, circulating progenitors were able to participate in muscle regeneration, though in very small percentage. Searching for the embryonic origin of these progenitors, we identified them as originating at least in part from the embryonic aorta and, at later stages, from the microvasculature of skeletal muscle. While continuing to investigate origin and fate of MABs, the fact that they could be expanded in vitro (also from human muscle) and cross the vessel wall, suggested a protocol for the cell therapy of muscular dystrophies. We tested this protocol in mice and dogs before proceeding to the first clinical trial on Duchenne Muscular Dystrophy patients that showed safety but minimal efficacy. In the last years, we have worked to overcome the problem of low engraftment and tried to understand their role as auxiliary myogenic progenitors during development and regeneration.
Funder
European Research Council
Subject
Genetics (clinical),Genetics,Molecular Medicine