Globular Adiponectin as a Complete Mesoangioblast Regulator: Role in Proliferation, Survival, Motility, and Skeletal Muscle Differentiation

Mol Biol Cell. 2010 Mar 15;21(6):848-59. doi: 10.1091/mbc.e09-04-0310. Epub 2010 Jan 20.

Abstract

Mesoangioblasts are progenitor endowed with multipotent mesoderm differentiation ability. Despite the promising results obtained with mesoangioblast transplantation in muscle dystrophy, an improvement of their efficient engrafting and survival within damaged muscles, as well as their ex vivo activation/expansion and commitment toward myogenic lineage, is highly needed and should greatly increase their therapeutic potential. We show that globular adiponectin, an adipokine endowed with metabolic and differentiating functions for muscles, regulates vital cues of mesoangioblast cell biology. The adipokine drives mesoangioblasts to entry cell cycle and strongly counteracts the apoptotic process triggered by growth factor withdrawal, thereby serving as an activating and prosurvival stem cell factor. In addition, adiponectin provides a specific protection against anoikis, the apoptotic death due to lack of anchorage to extracellular matrix, suggesting a key protective role for these nonresident stem cells after systemic injection. Finally, adiponectin behaves as a chemoattractive factor toward mature myotubes and stimulates their differentiation toward the skeletal muscle lineage, serving as a positive regulator in mesoangioblast homing to injured or diseased muscles. We conclude that adiponectin exerts several advantageous effects on mesoangioblasts, potentially valuable to improve their efficacy in cell based therapies of diseased muscles.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adiponectin / chemistry
  • Adiponectin / metabolism
  • Adiponectin / pharmacology*
  • Animals
  • Cell Differentiation / drug effects
  • Cell Differentiation / physiology
  • Cell Movement / drug effects*
  • Cell Movement / physiology
  • Cell Proliferation / drug effects*
  • Cell Survival / drug effects*
  • Cells, Cultured
  • Coculture Techniques
  • Humans
  • Mice
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Muscle, Skeletal / cytology
  • Muscle, Skeletal / drug effects
  • Muscle, Skeletal / physiology*
  • Rats
  • Sarcoglycans / genetics
  • Stem Cells / cytology
  • Stem Cells / drug effects*
  • Stem Cells / physiology*

Substances

  • Adiponectin
  • Sarcoglycans