Biofabricating murine and human myo-substitutes for rapid volumetric muscle loss restoration

Costantini, Marco; Testa, Stefano; Fornetti, Ersilia; Fuoco, Claudia; Nie, Minghao; Bernardini, Sergio; Rainer, Alberto; Baldi, Jacopo; Zoccali, Carmine; Biagini, R.; Castagnoli, Luisa; Vitiello, Libero; Blaauw, Bert; Seliktar, Dror; Święszkowski, Wojciech; Garstecki, Piotr; Takeuchi, Shoji; Cannata, Stefano; Gargioli, Cesare

doi:10.1101/2020.05.25.114819

Cited by 2 publications

(3 citation statements)

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“…Bones rather originate from ventral somite in the trunk, lateral mesoderm in the limbs and neural crest in the head. This notion came from pioneering chick-quail transplantation studies (Couly et al, 1993;Monsoro-Burq et al, 1994;Chevallier et al, 1977;Christ et al, 1977).…”

Section: The Developmental Origin Of Myogenic and Osteogenic Cellsmentioning

confidence: 99%

“…A bio-fabrication approach to restore skeletal muscle loss has been achieved using MABs (Costantini et al, 2021) and the latter are a valuable stem cell source to generate neuromuscular junction models in microfluidic devices (Stoklund Dittlau et al, 2021). These bidimensional cell systems are of great help to study cell-cell interactions and cell signalling and can be genetically manipulated (Santoni de Sio et al, 2008); however, more complex three-dimensional structures are necessary to better mimic the original muscle tissues and to contribute to the maturation of iPS cell derivatives.…”

Section: Mesoangioblasts Single Cell Omics and Modelling Muscle Patho...mentioning

confidence: 99%

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

et al. 2023

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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.

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Section: The Developmental Origin Of Myogenic and Osteogenic Cellsmentioning

confidence: 99%

Section: Mesoangioblasts Single Cell Omics and Modelling Muscle Patho...mentioning

confidence: 99%

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

et al. 2023

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“…Note, during implantation, the biofabricated myosubstitutes favored the formation of new blood vessels and neuromuscular junctions -essential aspects for cell survival and muscle contractile functions -as well as advanced muscle mass and recovery of muscle mass strength. Overall, these strategies represent a solid foundation with further testing and improvements for large animal myosubstitutes, which can be successfully translated into a promising platform in clinical scenarios for reconstructive therapy for patients with VML [124].…”

Section: Treatment Of Volumetric Muscle Injurymentioning

confidence: 99%

Skeletal Muscles: Insight into Embryonic Development, Satellite Cells, Histology, Ultrastructure, Innervation, Contraction and Relaxation, Causes, Pathophysiology, and Treatment of Volumetric Muscle I

Azab¹

2021

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Background: Skeletal muscles are attached to bone and are responsible for the axial and appendicular movement of the skeleton and for maintenance of body position and posture. Objectives: The present review aimed to high light on embryonic development of skeletal muscles, histological and ultrastructure, innervation, contraction and relaxation, causes, pathophysiology, and treatment of volumetric muscle injury. The heterogeneity of the muscle fibers is the base of the flexibility which allows the same muscle to be used for various tasks from continuous low-intensity activity, to repeated submaximal contractions, and to fast and strong maximal contractions. The formation of skeletal muscle begins during the fourth week of embryonic development as specialized mesodermal cells, termed myoblasts. As growth of the muscle fibers continues, aggregation into bundles occurs, and by birth, myoblast activity has ceased. Satellite cells (SCs), have single nuclei and act as regenerative cells. Satellite cells are the resident stem cells of skeletal muscle; they are considered to be self-renewing and serve to generate a population of differentiation-competent myoblasts that will participate as needed in muscle growth, repair, and regeneration. Based on various structural and functional characteristics, skeletal muscle fibres are classified into three types: Type I fibres, Type II-B fibres, and type II-A fibres. Skeletal muscle fibres vary in colour depending on their content of myoglobin. Each myofibril exhibits a repeating pattern of cross-striations which is a product of the highly ordered arrangement of the contractile proteins within it. The parallel myofibrils are arranged with their cross-striations in the register, giving rise to the regular striations seen with light microscopy in longitudinal sections of skeletal muscle. Each skeletal muscle receives at least two types of nerve fibers: motor and sensory. Striated muscles and myotendinous junctions contain sensory receptors that are encapsulated proprioceptors. The process of contraction, usually triggered by neural impulses, obeys the all-or-none law. During muscle contraction, the thin filaments slide past the thick filaments, as proposed by Huxley's sliding filament theory. In response to a muscle injury, SCs are activated and start to proliferate; at this stage, they are often referred to as either myogenic precursor cells (MPC) or myoblasts. In vitro, evidence has been presented that satellite cells can be pushed towards the adipogenic and osteogenic lineages, but contamination of such cultures from non-myogenic cells is sometimes hard to dismiss as the underlying cause of this observed multipotency. There are, however, other populations of progenitors isolated from skeletal muscle, including endothelial cells and muscle-derived stem cells (MDSCs), blood-vessel-associated mesoangioblasts, muscle side-population cells, CD133+ve cells, myoendothelial cells, and pericytes. Volumetric muscle loss (VML) is defined as the traumatic or surgical loss of skeletal muscle with resultant functional impairment. It represents a challenging clinical problem for both military and civilian medicine. VML results in severe cosmetic deformities and debilitating functional loss. In response to damage, skeletal muscle goes through a well-defined series of events including; degeneration (1 to 3days), inflammation, and regeneration (3 to 4 weeks), fibrosis, and extracellular matrix remodeling (3 to 6 months).. Mammalian skeletal muscle has an impressive ability to regenerate itself in response to injury. During muscle tissue repair following damage, the degree of damage and the interactions between muscle and the infiltrating inflammatory cells appear to affect the successful outcome of the muscle repair process. The transplantation of stem cells into aberrant or injured tissue has long been a central goal of regenerative medicine and tissue engineering. Conclusion: It can be concluded that the formation of skeletal muscle begins during the fourth week of embryonic development as specialized mesodermal cells, termed myoblasts, by birth myoblast activity has ceased. Satellite cells are considered to be self-renewing, and serve to generate a population of differentiation-competent myoblasts. Skeletal muscle fibres are classified into three types. The process of contraction, usually triggered by neural impulses, obeys the all-or-none law. VML results in severe cosmetic deformities and debilitating functional loss. Mammalian skeletal muscle has an impressive ability to regenerate itself in response to injury. The transplantation of stem cells into aberrant or injured tissue has long been a central goal of regenerative medicine and tissue engineering.

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Biofabricating murine and human myo-substitutes for rapid volumetric muscle loss restoration

Cited by 2 publications

References 58 publications

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

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

Skeletal Muscles: Insight into Embryonic Development, Satellite Cells, Histology, Ultrastructure, Innervation, Contraction and Relaxation, Causes, Pathophysiology, and Treatment of Volumetric Muscle I

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