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

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.

Molecular mechanisms and therapeutic strategies for neuromuscular diseases

“…Given the complexities associated with achieving satisfactory integration into affected muscles, current research in cell-based therapies is focusing on harnessing secondary effects rather than primarily rescuing muscle integrity. For instance, engineered mesangioblasts hold promise to facilitate exon skipping without the necessity for repeated infusions [ 179 ].…”

Developmental Biology: from genes to functional organism – news from the 3rd Meeting of the Visegrád Group Society for Developmental Biology

“…During his invited lecture, giulio Cossu (University of Manchester, Uk and san raffaele Hospital, italy) demonstrated that mesoangioblasts, derived from adventitial pericytes of skeletal muscle, may be promising candidates for therapies of muscular dystrophies. recently, giulio's team has developed a new strategy that compensates for the low engraftment of transplanted mesoangioblasts in patients' muscles by genetically amplifying their dystrophin production (Cossu et al, 2023) and now works on immune-privileged mesoangioblasts as universal donor cells. The next speaker, radek sindelka (institute of Biotechnology, Czech academy of sciences, Czech republic), opened the floor for short, and thematically diverse, talks.…”