Mesoangioblasts at 20: From the embryonic aorta to the patient bed

Giulio Cossu, Rossana Tonlorenzi, Silvia Brunelli, Maurilio Sampaolesi, Graziella Messina, Emanuele Azzoni, Sara Benedetti, Stefano Biressi, Chiara Bonfanti, Laricia Bragg, Jordi Camps, Ornella Cappellari, Marco Cassano, Fabio Ciceri, Marcello Coletta, Diego Covarello, Stefania Crippa, M. Gabriella Cusella-De Angelis, Luciana De Angelis, Arianna Dellavalle, Jordi Diaz-Manera, Daniela Galli, Francesco Galli, Cesare Gargioli, Mattia F. M. Gerli, Giorgia Giacomazzi, Beatriz G. Galvez, Hidetoshi Hoshiya, Maria Guttinger, Anna Innocenzi, M. Giulia Minasi, Laura Perani, Stefano C Previtali, Mattia Quattrocelli, Martina Ragazzi, Urmas Roostalu, Giuliana Rossi, Raffaella Scardigli, Dario Sirabella, Francesco Saverio Tedesco, Yvan Torrente and Gonzalo Ugarte.


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.