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KMID : 0578320190420090661
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Molecules and Cells
2019 Volume.42 No. 9 p.661 ~ p.671
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Small Molecule-Based Strategy Promotes Nucleus Pulposus Specific Differentiation of Adipose-Derived Mesenchymal Stem Cells
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Hua Jianming
Shen Ning
Wang Jingkai
Tao Yiqing
Li Fangcai
Chen Qixin
Zhou Xiaopeng
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Abstract
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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-β3 (TGF-β3) 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-β3. 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.
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KEYWORD
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adipose-derived mesenchymal stem cell, differentiation, nucleus pulposus, Smoothened Agonist, transforming growth factor-β3
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