Molecules and Cells

Korean Society for Molecular and Cellular Biology (한국분자세포생물학회)
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Small Molecule-Based Strategy Promotes Nucleus Pulposus Specific Differentiation of Adipose-Derived Mesenchymal Stem Cells

  • Hua, Jianming (Department of Radiology, 2nd Affiliated Hospital, School of Medicine, Zhejiang University) ;
  • Shen, Ning (Department of Rheumatology, Sir Run Run Shaw Hospital, School of Medicine, Zhejiang University) ;
  • Wang, Jingkai (Department of Orthopedics Surgery, 2nd Affiliated Hospital, School of Medicine, Zhejiang University) ;
  • Tao, Yiqing (Department of Orthopedics Surgery, 2nd Affiliated Hospital, School of Medicine, Zhejiang University) ;
  • Li, Fangcai (Department of Orthopedics Surgery, 2nd Affiliated Hospital, School of Medicine, Zhejiang University) ;
  • Chen, Qixin (Department of Orthopedics Surgery, 2nd Affiliated Hospital, School of Medicine, Zhejiang University) ;
  • Zhou, Xiaopeng (Department of Orthopedics Surgery, 2nd Affiliated Hospital, School of Medicine, Zhejiang University)
  • Received : 2019.05.19
  • Accepted : 2019.08.21
  • Published : 2019.09.30
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Abstract

Adipose tissue-derived mesenchymal stem cells (ADSCs) are promising for regenerating degenerated intervertebral discs (IVDs), but the low efficiency of nucleus pulposus (NP)-specific differentiation limits their clinical applications. The Sonic hedgehog (Shh) signaling pathway is important in NP-specific differentiation of ADSCs, and Smoothened Agonist (SAG) is a highly specific and effective agonist of Shh signaling. In this study, we proposed a new differentiation strategy with the use of the small molecule SAG. The NP-specific differentiation and extracellular matrix (ECM) synthesis of ADSCs were measured in vitro, and the regenerative effects of SAG pretreated ADSCs in degenerated IVDs were verified in vivo. The results showed that the combination of SAG and transforming growth factor-${\beta}3$ ($TGF-{\beta}3$) is able to increase the ECM synthesis of ADSCs. In addition, the gene and protein expression levels of NP-specific markers were increased by treatment with SAG and $TGF-{\beta}3$. Furthermore, SAG pretreated ADSCs can also improve the disc height, water content, ECM content, and structure of degenerated IVDs in vivo. Our new differentiation scheme has high efficiency in inducing NP-specific differentiation of ADSCs and is promising for stem cell-based treatment of degenerated IVDs.

Keywords

References

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