In vivo generation of a mature and functional artificial skeletal muscle

• Published in: EMBO molecular medicine 2015-04, Vol.7 (4), p.411-422
• Main Authors: Fuoco, Claudia, Rizzi, Roberto, Biondo, Antonella, Longa, Emanuela, Mascaro, Anna, Shapira‐Schweitzer, Keren, Kossovar, Olga, Benedetti, Sara, Salvatori, Maria L, Santoleri, Sabrina, Testa, Stefano, Bernardini, Sergio, Bottinelli, Roberto, Bearzi, Claudia, Cannata, Stefano M, Seliktar, Dror, Cossu, Giulio, Gargioli, Cesare
• Format: Article
• Language: English
• Subjects: Angiogenesis; Animals; artificial skeletal muscle; Cells, Immobilized - metabolism; Cells, Immobilized - transplantation; EMBO25; EMBO34; Experiments; Fibrinogen; Heterografts; Humans; Hydrogels; Kinases; Maturation; mesoangioblasts; Mice; Mice, Transgenic; Microscopy; Muscle, Skeletal - blood supply; Muscle, Skeletal - metabolism; Muscle, Skeletal - transplantation; Musculoskeletal system; Neovascularization, Physiologic; Nerves; PEG‐fibrinogen; Placenta; Research Article; Skeletal muscle; Skin; Survival; Tissue engineering
• ISSN: 1757-4676; 1757-4684
• DOI: 10.15252/emmm.201404062

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. Synopsis This study proposes a novel and efficient strategy for skeletal muscle tissue engineering based on in vitro mixing of mouse or human mesoangioblasts with a PEG‐fibrinogen, which promotes their survival and differentiation into muscle. Upon graft implantation between the skin and the outer surface of the tibialis anterior , mature and aligned myofibres formed within a few weeks as a complete and functional extra muscle. Upon graft replacement of an almost completely ablated tibialis anterior , a new skeletal muscle very similar to the ablated one formed within a few weeks. Placental‐derived growth factor‐lentivirus transduction of muscle cells prior to transplant stimulates blood vessel growth and contributes to in vivo cells survival and maturation. This novel strategy opens up the possibility for patient‐specific muscle engineering in a large number of pathological conditions involving muscle tissue wasting. Graphical Abstract This study proposes a novel and efficient strategy for skeletal muscle tissue engineering based on in vitro mixing of mouse or human mesoangioblasts with a PEG‐fibrinogen, which promotes their survival and differentiation into muscle.