Transplantation of Adipose Stromal Cell Sheet Producing Hepatocyte Growth Factor Induces Pleiotropic Effect in Ischemic Skeletal Muscle

Int J Mol Sci. 2019 Jun 24;20(12):3088. doi: 10.3390/ijms20123088.


Cell therapy remains a promising approach for the treatment of cardiovascular diseases. In this regard, the contemporary trend is the development of methods to overcome low cell viability and enhance their regenerative potential. In the present study, we evaluated the therapeutic potential of gene-modified adipose-derived stromal cells (ADSC) that overexpress hepatocyte growth factor (HGF) in a mice hind limb ischemia model. Angiogenic and neuroprotective effects were assessed following ADSC transplantation in suspension or in the form of cell sheet. We found superior blood flow restoration, tissue vascularization and innervation, and fibrosis reduction after transplantation of HGF-producing ADSC sheet compared to other groups. We suggest that the observed effects are determined by pleiotropic effects of HGF, along with the multifactorial paracrine action of ADSC which remain viable and functionally active within the engineered cell construct. Thus, we demonstrated the high therapeutic potential of the utilized approach for skeletal muscle recovery after ischemic damage associated with complex tissue degenerative effects.

Keywords: adipose derived stromal cells; angiogenesis; cell sheet; hepatocyte growth factor; hind limb ischemia; reinnervation; skeletal muscle regeneration.

MeSH terms

  • Adipose Tissue / cytology*
  • Animals
  • Cell Culture Techniques
  • Cell Differentiation / genetics
  • Cell Movement / drug effects
  • Culture Media, Conditioned / pharmacology
  • Disease Models, Animal
  • Gene Expression
  • Hepatocyte Growth Factor / biosynthesis*
  • Hepatocyte Growth Factor / genetics
  • Humans
  • Ischemia
  • Mice
  • Muscle Fibers, Skeletal / cytology*
  • Muscle Fibers, Skeletal / metabolism*
  • Muscle, Skeletal / blood supply*
  • Muscle, Skeletal / drug effects
  • Muscle, Skeletal / metabolism*
  • Muscle, Skeletal / pathology
  • Neovascularization, Physiologic / drug effects
  • Neovascularization, Physiologic / genetics
  • Neuroglia / cytology
  • Neuroglia / drug effects
  • Neuroglia / metabolism
  • Neuronal Outgrowth / drug effects
  • Stromal Cells / metabolism*
  • Stromal Cells / transplantation*


  • Culture Media, Conditioned
  • Hepatocyte Growth Factor