Growth factor supplemented matrigel improves ectopic skeletal muscle formation - A cell therapy approach

Andrea Barbero, Roberto Benelli, Simona Minghelli, Francesca Tosetti, Alessandra Dorcaratto, Carola Ponzetto, Anton Wernig, Michael J. Cullen, Adriana Albini, Douglas M. Noonan

Research output: Contribution to journalArticle

40 Citations (Scopus)

Abstract

Following damage to skeletal muscle, satellite cells become activated, migrate towards the injured area, proliferate, and fuse with each other to form myotubes which finally mature into myofibers. We tested a new approach to muscle regeneration by incorporating myoblasts, with or without the exogenous growth factors bFGF or HGF, into three-dimensional gels of reconstituted basement membrane (matrigel). In vitro, bFGF and HGF induced C2C12 myoblast proliferation and migration and were synergistic when used together. In vivo, C2C12 or primary i28 myoblasts were injected subcutaneously together with matrigel and growth factors in the flanks of nude mice. The inclusion of either bFGF or HGF increased the vascularization of the gets. Gels supplemented with bFGF showed myogenesis accompanied by massive mesenchymal cell recruitment and poor organization of the fascicles. Samples containing HGF showed delayed differentiation with respect to controls or bFGF, with increased myoblast proliferation and a significantly higher numbers of cells in myotubes at later time points. HGF samples showed limited mesenchymal cell infiltration and relatively good organization of fascicles. The use of both bFGF and HGF together showed increased numbers of nuclei in myotubes, but with bFGF-mediated fibroblast recruitment dominating. These studies suggest that an appropriate combination of basement membrane components and growth factors could represent a possible approach to enhance survival dispersion, proliferation, and differentiation of myogenic cells during muscle regeneration and/or myoblast transplantation. This model will help develop cell therapy of muscle diseases and open the future to gene therapy approaches.

Original languageEnglish
Pages (from-to)183-192
Number of pages10
JournalJournal of Cellular Physiology
Volume186
Issue number2
DOIs
Publication statusPublished - 2001

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Myoblasts
Cell- and Tissue-Based Therapy
Muscle
Intercellular Signaling Peptides and Proteins
Skeletal Muscle
Skeletal Muscle Fibers
Basement Membrane
Gels
Regeneration
Gene therapy
Skeletal Muscle Satellite Cells
Electric fuses
Fibroblasts
Muscles
Infiltration
Muscle Development
Nude Mice
Genetic Therapy
Muscle Cells
Cells

ASJC Scopus subject areas

  • Clinical Biochemistry
  • Cell Biology
  • Physiology

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Growth factor supplemented matrigel improves ectopic skeletal muscle formation - A cell therapy approach. / Barbero, Andrea; Benelli, Roberto; Minghelli, Simona; Tosetti, Francesca; Dorcaratto, Alessandra; Ponzetto, Carola; Wernig, Anton; Cullen, Michael J.; Albini, Adriana; Noonan, Douglas M.

In: Journal of Cellular Physiology, Vol. 186, No. 2, 2001, p. 183-192.

Research output: Contribution to journalArticle

Barbero, Andrea ; Benelli, Roberto ; Minghelli, Simona ; Tosetti, Francesca ; Dorcaratto, Alessandra ; Ponzetto, Carola ; Wernig, Anton ; Cullen, Michael J. ; Albini, Adriana ; Noonan, Douglas M. / Growth factor supplemented matrigel improves ectopic skeletal muscle formation - A cell therapy approach. In: Journal of Cellular Physiology. 2001 ; Vol. 186, No. 2. pp. 183-192.
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