Skeletal Myogenic Progenitors Originating from Embryonic Dorsal Aorta Coexpress Endothelial and Myogenic Markers and Contribute to Postnatal Muscle Growth and Regeneration

Skeletal muscle in vertebrates is derived from somites, epithelial structures of the paraxial mesoderm, yet many unrelated reports describe the occasional appearance of myogenic cells from tissues of nonsomite origin, suggesting either transdifferentiation or the persistence of a multipotent progenitor. Here, we show that clonable skeletal myogenic cells are present in the embryonic dorsal aorta of mouse embryos. This finding is based on a detailed clonal analysis of different tissue anlagen at various developmental stages. In vitro, these myogenic cells show the same morphology as satellite cells derived from adult skeletal muscle, and express a number of myogenic and endothelial markers. Surprisingly, the latter are also expressed by adult satellite cells. Furthermore, it is possible to clone myogenic cells from limbs of mutant c-Met-/- embryos, which lack appendicular muscles, but have a normal vascular system. Upon transplantation, aorta-derived myogenic cells participate in postnatal muscle growth and regeneration, and fuse with resident satellite cells. The potential of the vascular system to generate skeletal muscle cells may explain observations of nonsomite skeletal myogenesis and raises the possibility that a subset of satellite cells may derive from the vascular system

Met-activating genetically improved chimeric factor-1 promotes angiogenesis and hypertrophy in adult myogenesis

BACKGROUND: Myogenic progenitor cells (activated satellite cells) are able to express both HGF and its receptor cMet. After muscle injury, HGF-Met stimulation promotes activation and primary division of satellite cells. MAGIC-F1 (Met-Activating Genetically Improved Chimeric Factor-1) is an engineered protein that contains two human Met-binding domains that promotes muscle hypertrophy. MAGIC-F1 protects myogenic precursors against apoptosis and increases their fusion ability enhancing muscle differentiation. Hemizygous and homozygous Magic-F1 transgenic mice displayed constitutive muscle hypertrophy. METHODS: Here we describe microarray analysis on Magic-F1 myogenic progenitor cells showing an altered gene signatures on muscular hypertrophy and angiogenesis compared to wild-type cells. In addition, we performed a functional analysis on Magic-F1+/+ transgenic mice versus controls using treadmill test. RESULTS: We demonstrated that Magic-F1+/+ mice display an increase in muscle mass and cross-sectional area leading to an improvement in running performance. Moreover, the presence of MAGIC-F1 affected positively the vascular network, increasing the vessel number in fast twitch fibers. Finally, the gene expression profile analysis of Magic-F1+/+ satellite cells evidenced transcriptomic changes in genes involved in the control of muscle growth, development and vascularisation. CONCLUSION: We showed that MAGIC -F1-induced muscle hypertrophy affects positively vascular network, increasing vessel number in fast twitch fibers. This was due to unique features of mammalian skeletal muscle and its remarkable ability to adapt promptly to different physiological demands by modulating the gene expression profile in myogenic progenitors

Ultrasound stimulus to enhance the bone regeneration capability of gelatin cryogels

In the present study, gelatin-based cryogels have been seeded with human SAOS-2 osteoblasts. In order to overcome the drawbacks associated with in vitro culture systems, such as limited diffusion and inhomogeneous cell-matrix distribution, this work describes the application of ultrasounds (average power, 149 mW; frequency, 1.5 MHz) to physically enhance the cell culture in vitro. The results indicate that the physical stimulation of cell-seeded gelatin-based cryogels upregulates the bone matrix production

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

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

Magic-factor 1, a partial agonist of Met, induces muscle hypertrophy by protecting myogenic progenitors from apoptosis.

Hepatocyte Growth Factor (HGF) is a pleiotropic cytokine of mesenchymal origin that mediates a characteristic array of biological activities including cell proliferation, survival, motility and morphogenesis. Its high affinity receptor, the tyrosine kinase Met, is expressed by a wide range of tissues and can be activated by either paracrine or autocrine stimulation. Adult myogenic precursor cells, the so called satellite cells, express both HGF and Met. Following muscle injury, autocrine HGF-Met stimulation plays a key role in promoting activation and early division of satellite cells, but is shut off in a second phase to allow myogenic differentiation. In culture, HGF stimulation promotes proliferation of muscle precursors thereby inhibiting their differentiation

Why to open an Institute of Anatomy to the public: opportunities for socially useful interactions.

In 1772 Antonio Scarpa (1752-1832), one of the most famous surgeons and anatomists in the world, started to prepare and collect natural preparations which included anatomical statues or body parts made from real corps. In his Index Rerum Musei Anatomici Ticinenis [1], he listed 350 speciments. This collection, thanks to Scarpa’s successors Bartolomeo Panizza (1785-1867) and Giovanni Zoja (1833-1899), was enlarged and used for lectures in a span of over one hundred and fifty years. This very precious collection, still preserved by the Anatomical Institute [2] of the University of Pavia, in the last years was the subject of renewed interest from when a certain number of students of the Medical Course were allowed to visit the collection. Thanks to the student’s enthusiasm, on March 2018 the anatomical collection was open to the public during the initiative “F.A.I. Spring Days”. In the course of 2019, it also was possible to organize some visits for local primary and high school students. Besides, the Centro Orientamento (C.OR.) of Pavia supports students by promoting their integration into the University system. In the last two years, in collaboration with C.OR., we organized different activities aimed at giving students information about ours Medical Courses and, during the INFODAY, the Anatomical Room and Collection represent one of the most stimulating moments for students. Visits offered a guided tours of our Institute allowing the vision of the Collection and practical experience on plastic 3D models. Finally, visitors and students can experience the use of Anatomage. Today in Italian universities dissection may not be economically feasible as it once was but, if combined with models and with the latest digital 3D modelling tools, prosecution component and digital dissection may be incorporated into any syllabus. These means certainly won’t replace a cadaver but they can assist students in visually conceptualizing complicated anatomical systems in a new-and cost effective way. Finally, in modern society the body is often shown and used incorrectly and in a misleadingly way. Opening Anatomy Institutes to the public during specially organized events could provide the public's curiosity with appropriate answers, reaffirming the value of anatomical discipline, science and knowledge and sensitize the population to body donation for study and research purposes. In this process, Medical Students can provide us qualified and enthusiastic help

Attività sport-specifica nel pre-adolescente: un approccio sperimentale

Scopo: il problema della specializzazione precoce nello sport e dei possibili rischi per la salute psico-fisica del preadolescente, a volte ancora oggetto di discussione nell’ambito della ricerca, ha dato lo spunto alla realizzazione del presente lavoro. L’obiettivo è stato quello di valutare gli effetti determinati dall’inserimento di esercitazioni speciali (kihon, karate) in un programma di attività motoria multilaterale in bambini di scuola primaria. Materiali e Metodi: ottantadue bambini sono stati casualmente divisi in 4 gruppi in base al sesso e al fatto di svolgere solo attività multilaterale (Controlli: Cf, 19 F, 6,4 ± 0,3 a; Cm, 22 M, 6,3 ± 0,3 a) o anche una parte di esercitazioni sport-specifiche (Speciali: Sf, 20 F, 6,3 ± 0,3 a; Sm, 21 M, 6,4 ± 0,3 a). L’attività è stata svolta per otto settimane con sedute bisettimanali di 60 minuti ciascuna. Prima e dopo il periodo di lavoro tutti i soggetti sono stati sottoposti a una serie di test motori standardizzati. Risultati: tutti i gruppi sono migliorati significativamente (p < 0,05) rispetto alla loro situazione iniziale, mentre il confronto tra i gruppi Speciali e i Controlli non ha mostrato differenze significative, a eccezione del parametro legato all’equilibrio statico. Conclusioni: dai risultati sembra che l’introduzione di esercitazioni speciali opportunamente modulate, oltre a non creare problemi di natura psico-fisica, possa essere un ausilio ulteriore al miglioramento delle capacità motorie di base del bambino. Parole chiave: specializzazione precoce - attività multilaterale - equilibrio static