Directed differentiation of skin-derived precursors into functional vascular smooth muscle cells

  • Steinbach S
  • El-Mounayri O
  • Dacosta R
 et al. 
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OBJECTIVE The goal of this study was to characterize the factors and conditions required for smooth muscle cell (SMC)-directed differentiation of Sox2(+) multipotent rat and human skin-derived precursors (SKPs) and to define whether they represent a source of fully functional vascular SMCs for applications in vivo. METHODS AND RESULTS We found that rat SKPs can differentiate almost exclusively into SMCs by reducing serum concentrations to 0.5% to 2% and plating them at low density. Human SKPs derived from foreskin required the addition of transforming growth factor-β1 or -β3 to differentiate into SMCs, but they did so even in the absence of serum. SMC formation was confirmed by quantitative reverse transcription-polymerase chain reaction, immunocytochemistry, and fluorescence-activated cell sorting, with increased expression of smoothelin-B and little to no expression of telokin or smooth muscle γ-actin, together indicating that SKPs differentiated into vascular rather than visceral SMCs. Rat and human SKP-derived SMCs were able to contract in vitro and also wrap around and support new capillary and larger blood vessel formation in angiogenesis assays in vivo. CONCLUSIONS SKPs are Sox2(+) progenitors that represent an attainable autologous source of stem cells that can be easily differentiated into functional vascular SMCs in defined serum-free conditions without reprogramming. SKPs represent a clinically viable cell source for potential therapeutic applications in neovascularization.

Author-supplied keywords

  • angiogenesis
  • differentiation
  • skin-derived precursors
  • vascular biology
  • vascular muscle

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  • Sarah K. Steinbach

  • Omar El-Mounayri

  • Ralph S. Dacosta

  • Matthew J. Frontini

  • Zengxuan Nong

  • Azusa Maeda

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