Myogenic induction of adult and pluripotent stem cells using recombinant proteins

Biochem Biophys Res Commun. 2015 Aug 28;464(3):755-61. doi: 10.1016/j.bbrc.2015.07.022. Epub 2015 Jul 8.

Abstract

Met Activating Genetically Improved Chimeric Factor 1 (Magic-F1) is a human recombinant protein, derived from dimerization of the receptor-binding domain of hepatocyte growth factor. Previous experiments demonstrate that in transgenic mice, the skeletal muscle specific expression of Magic-F1 can induce a constitutive muscular hypertrophy, improving running performance and accelerating muscle regeneration after injury. In order to evaluate the therapeutic potential of Magic-F1, we tested its effect on multipotent and pluripotent stem cells. In murine mesoangioblasts (adult vessel-associated stem cells), the presence of Magic-F1 did not alter their osteogenic, adipogenic or smooth muscle differentiation ability. However, when analyzing their myogenic potential, mesoangioblasts expressing Magic-F1 differentiated spontaneously into myotubes. Finally, Magic-F1 inducible cassette was inserted into a murine embryonic stem cell line by homologous recombination. When embryonic stem cells were subjected to myogenic differentiation, the presence of Magic-F1 resulted in the upregulation of Pax3 and Pax7 that enhanced the myogenic commitment of transgenic pluripotent stem cells. Taken together our results candidate Magic-F1 as a potent myogenic stimulator, able to enhance muscular differentiation from both adult and pluripotent stem cells.

Keywords: Embryonic stem cells; Magic-F1; Mesoangioblast; Myogenic differentiation; Recombinant protein.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult Stem Cells / cytology*
  • Adult Stem Cells / physiology*
  • Animals
  • Cell Differentiation / genetics
  • Cell Differentiation / physiology
  • Cell Line
  • Green Fluorescent Proteins / genetics
  • Green Fluorescent Proteins / metabolism
  • HEK293 Cells
  • Hepatocyte Growth Factor / genetics
  • Hepatocyte Growth Factor / metabolism
  • Humans
  • Mice
  • Mice, Transgenic
  • Muscle Development / genetics
  • Muscle Development / physiology*
  • PAX3 Transcription Factor
  • PAX7 Transcription Factor / genetics
  • Paired Box Transcription Factors / genetics
  • Pluripotent Stem Cells / cytology*
  • Pluripotent Stem Cells / physiology*
  • Recombinant Proteins / genetics*
  • Recombinant Proteins / metabolism*
  • Up-Regulation

Substances

  • HGF protein, human
  • PAX3 Transcription Factor
  • PAX7 Transcription Factor
  • Paired Box Transcription Factors
  • Pax7 protein, mouse
  • Recombinant Proteins
  • magic-factor 1 protein, mouse
  • Pax3 protein, mouse
  • Green Fluorescent Proteins
  • Hepatocyte Growth Factor