title: In vivo generation of a mature and functional artificial skeletal muscle.
abstract: Extensive loss of skeletal muscle tissue results in mutilations and severe loss of function. In vitro-generated artificial muscles undergo necrosis when transplanted in vivo before host angiogenesis may provide oxygen for fibre survival. Here, we report a novel strategy based upon the use of mouse or human mesoangioblasts encapsulated inside PEG-fibrinogen hydrogel. Once engineered to express placental-derived growth factor, mesoangioblasts attract host vessels and nerves, contributing to in vivo survival and maturation of newly formed myofibres. When the graft was implanted underneath the skin on the surface of the tibialis anterior, mature and aligned myofibres formed within several weeks as a complete and functional extra muscle. Moreover, replacing the ablated tibialis anterior with PEG-fibrinogen-embedded mesoangioblasts also resulted in an artificial muscle very similar to a normal tibialis anterior. This strategy opens the possibility for patient-specific muscle creation for a large number of pathological conditions involving muscle tissue wasting.
authors.affiliation: Department of Biology, Tor Vergata Rome University, Rome, Italy.
authors.forename: Claudia
authors.initials: C
authors.lastname: Fuoco
authors.affiliation: IRCCS MultiMedica, Milan, Italy Cell Biology and Neurobiology Institute, National Research Council of Italy, Rome, Italy.
authors.forename: Roberto
authors.initials: R
authors.lastname: Rizzi
authors.affiliation: Department of Biology, Tor Vergata Rome University, Rome, Italy.
authors.forename: Antonella
authors.initials: A
authors.lastname: Biondo
authors.affiliation: Department of Molecular Medicine and Interdepartmental Centre for Research in Sport Biology and Medicine, University of Pavia, Pavia, Italy.
authors.forename: Emanuela
authors.initials: E
authors.lastname: Longa
authors.affiliation: Department of Molecular Medicine and Interdepartmental Centre for Research in Sport Biology and Medicine, University of Pavia, Pavia, Italy.
authors.forename: Anna
authors.initials: A
authors.lastname: Mascaro
authors.affiliation: Faculty of Biomedical Engineering, Technion-Israel Institute of Technology, Haifa, Israel.
authors.forename: Keren
authors.initials: K
authors.lastname: Shapira-Schweitzer
authors.affiliation: Faculty of Biomedical Engineering, Technion-Israel Institute of Technology, Haifa, Israel.
authors.forename: Olga
authors.initials: O
authors.lastname: Kossovar
authors.affiliation: Department of Cell and Developmental Biology, University College London, London, UK.
authors.forename: Sara
authors.initials: S
authors.lastname: Benedetti
authors.affiliation: Department of Biology, Tor Vergata Rome University, Rome, Italy.
authors.forename: Maria L
authors.initials: ML
authors.lastname: Salvatori
authors.affiliation: Department of Biology, Tor Vergata Rome University, Rome, Italy.
authors.forename: Sabrina
authors.initials: S
authors.lastname: Santoleri
authors.affiliation: Department of Biology, Tor Vergata Rome University, Rome, Italy.
authors.forename: Stefano
authors.initials: S
authors.lastname: Testa
authors.affiliation: Department of Biology, Tor Vergata Rome University, Rome, Italy.
authors.forename: Sergio
authors.initials: S
authors.lastname: Bernardini
authors.affiliation: Department of Molecular Medicine and Interdepartmental Centre for Research in Sport Biology and Medicine, University of Pavia, Pavia, Italy Fondazione Salvatore Maugeri (IRCCS), Scientific Institute of Pavia, Pavia, Italy.
authors.forename: Roberto
authors.initials: R
authors.lastname: Bottinelli
authors.affiliation: IRCCS MultiMedica, Milan, Italy Cell Biology and Neurobiology Institute, National Research Council of Italy, Rome, Italy.
authors.forename: Claudia
authors.initials: C
authors.lastname: Bearzi
authors.affiliation: Department of Biology, Tor Vergata Rome University, Rome, Italy cesare.gargioli@uniroma2.it giulio.cossu@manchester.ac.uk cannata@uniroma2.it.
authors.forename: Stefano M
authors.initials: SM
authors.lastname: Cannata
authors.affiliation: Faculty of Biomedical Engineering, Technion-Israel Institute of Technology, Haifa, Israel.
authors.forename: Dror
authors.initials: D
authors.lastname: Seliktar
authors.affiliation: Department of Cell and Developmental Biology, University College London, London, UK Institute of Inflammation and Repair, University of Manchester, Manchester, UK cesare.gargioli@uniroma2.it giulio.cossu@manchester.ac.uk cannata@uniroma2.it.
authors.forename: Giulio
authors.initials: G
authors.lastname: Cossu
authors.affiliation: Department of Biology, Tor Vergata Rome University, Rome, Italy IRCCS MultiMedica, Milan, Italy cesare.gargioli@uniroma2.it giulio.cossu@manchester.ac.uk cannata@uniroma2.it.
authors.forename: Cesare
authors.initials: C
authors.lastname: Gargioli
mesh_terms: D000818:Animals; D018914:Cells, Immobilized / Q000378:metabolism / Q000637:transplantation; D064593:Heterografts; D006801:Humans; D051379:Mice; D008822:Mice, Transgenic; D018482:Muscle, Skeletal / Q000098:blood supply / Q000378:metabolism / Q000637:transplantation; D018919:Neovascularization, Physiologic
keywords: PEG‐fibrinogen; artificial skeletal muscle; mesoangioblasts