title: Injected matrix stimulates myogenesis and regeneration of mouse skeletal muscle after ischaemic injury.
abstract: Biomaterial-guided regeneration represents a novel approach for the treatment of myopathies. Revascularisation and the intramuscular extracellular matrix are important factors in stimulating myogenesis and regenerating muscle damaged by ischaemia. In this study, we used an injectable collagen matrix, enhanced with sialyl LewisX (sLeX), to guide skeletal muscle differentiation and regeneration. The elastic properties of collagen and sLeX-collagen matrices were similar to those of skeletal muscle, and culture of pluripotent mESCs on the matrices promoted their differentiation into myocyte-like cells expressing Pax3, MHC3, myogenin and Myf5. The regenerative properties of matrices were evaluated in ischaemic mouse hind-limbs. Treatment with the sLeX-matrix augmented the production of myogenic-mediated factors insulin-like growth factor (IGF)-1, and IGF binding protein-2 and -5 after 3 days. This was followed by muscle regeneration, including a greater number of regenerating myofibres and increased transcription of Six1, M-cadherin, myogenin and Myf5 after 10 days. Simultaneously, the sLeX-matrix promoted increased mobilisation and engraftment of bone marrow-derived progenitor cells, the development of larger arterioles and the restoration of tissue perfusion. Both matrix treatments tended to reduce maximal forces of ischaemic solei muscles, but sLeX-matrix lessened this loss of force and also prevented muscle fatigue. Only sLeX-matrix treatment improved mobility of mice on a treadmill. Together, these results suggest a novel approach for regenerative myogenesis, whereby treatment only with a matrix, which possesses an inherent ability to guide myogenic differentiation of pluripotent stem cells, can enhance the endogenous vascular and myogenic regeneration of skeletal muscle, thus holding promise for future clinical use.
authors.affiliation: Division of Cardiac Surgery, University of Ottawa Heart Institute, 40 Ruskin Street, Ottawa, ON K1Y 4W7, Canada.
authors.forename: D
authors.initials: D
authors.lastname: Kuraitis
authors.forename: D
authors.initials: D
authors.lastname: Ebadi
authors.forename: P
authors.initials: P
authors.lastname: Zhang
authors.forename: E
authors.initials: E
authors.lastname: Rizzuto
authors.forename: B
authors.initials: B
authors.lastname: Vulesevic
authors.forename: D T
authors.initials: DT
authors.lastname: Padavan
authors.forename: A
authors.initials: A
authors.lastname: Al Madhoun
authors.forename: K A
authors.initials: KA
authors.lastname: McEwan
authors.forename: T
authors.initials: T
authors.lastname: Sofrenovic
authors.forename: K
authors.initials: K
authors.lastname: Nicholson
authors.forename: S C
authors.initials: SC
authors.lastname: Whitman
authors.forename: T G
authors.initials: TG
authors.lastname: Mesana
authors.forename: I S
authors.initials: IS
authors.lastname: Skerjanc
authors.forename: A
authors.initials: A
authors.lastname: Musarò
authors.forename: M
authors.initials: M
authors.lastname: Ruel
authors.forename: E J
authors.initials: EJ
authors.lastname: Suuronen
mesh_terms: D000818:Animals; D001672:Biocompatible Materials / Q000737:chemistry; D015820:Cadherins / Q000235:genetics; D002460:Cell Line; D003094:Collagen / Q000737:chemistry; D053595:Embryonic Stem Cells / Q000166:cytology; D005109:Extracellular Matrix / Q000737:chemistry / Q000637:transplantation*; D005260:Female; D015870:Gene Expression; D018398:Homeodomain Proteins / Q000235:genetics; D007334:Insulin-Like Growth Factor I / Q000235:genetics; D007511:Ischemia / Q000473:pathology; D008285:Major Histocompatibility Complex; D051379:Mice; D008810:Mice, Inbred C57BL; D024510:Muscle Development; D018482:Muscle, Skeletal / Q000098:blood supply / Q000378:metabolism / Q000502:physiology*; D051787:Myogenic Regulatory Factor 5 / Q000235:genetics; D018008:Myogenin / Q000235:genetics; D009844:Oligosaccharides / Q000737:chemistry; D000072041:PAX3 Transcription Factor; D051761:Paired Box Transcription Factors / Q000235:genetics; D012038:Regeneration; D000080506:Sialyl Lewis X Antigen
chemical_list: D001672:Biocompatible Materials; D015820:Cadherins; D018398:Homeodomain Proteins; C497418:Myf5 protein, mouse; C503801:Myog protein, mouse; D051787:Myogenic Regulatory Factor 5; D018008:Myogenin; D009844:Oligosaccharides; D000072041:PAX3 Transcription Factor; D051761:Paired Box Transcription Factors; D000080506:Sialyl Lewis X Antigen; C490947:Six1 protein, mouse; C519530:insulin-like growth factor-1, mouse; C068686:Pax3 protein, mouse; C070896:M-cadherin; D007334:Insulin-Like Growth Factor I; D003094:Collagen