Injected matrix stimulates myogenesis and regeneration of mouse skeletal muscle after ischaemic injury

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...

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Bibliographic Details
Published in:	European cells & materials Vol. 24; pp. 175 - 95; discussion 195-6
Main Authors:	Kuraitis, D, Ebadi, D, Zhang, P, Rizzuto, E, Vulesevic, B, Padavan, D T, Al Madhoun, A, McEwan, K A, Sofrenovic, T, Nicholson, K, Whitman, S C, Mesana, T G, Skerjanc, I S, Musarò, A, Ruel, M, Suuronen, E J
Format:	Journal Article
Language:	English
Published:	Switzerland Forum Multimedia Publishing LLC 12-09-2012
Subjects:	Animals Biocompatible Materials - chemistry Cadherins - genetics Cell Line Collagen - chemistry Embryonic Stem Cells - cytology Extracellular Matrix - chemistry Extracellular Matrix - transplantation Female Gene Expression Homeodomain Proteins - genetics Hydrogel injectable Insulin-Like Growth Factor I - genetics Ischemia - pathology Major Histocompatibility Complex Mice Mice, Inbred C57BL muscle Muscle Development Muscle, Skeletal - blood supply Muscle, Skeletal - metabolism Muscle, Skeletal - physiology Myogenic Regulatory Factor 5 - genetics Myogenin - genetics neovascularisation Oligosaccharides - chemistry Paired Box Transcription Factors - genetics PAX3 Transcription Factor Regeneration regenerative medicine tissue-material interactions
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Summary:	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.
Bibliography:	ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23
ISSN:	1473-2262 1473-2262
DOI:	10.22203/eCM.v024a13