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Mol Cells. 2019 Sep 30;42(9):661-671. doi: 10.14348/molcells.2019.0098.

Small Molecule-Based Strategy Promotes Nucleus Pulposus Specific Differentiation of Adipose-Derived Mesenchymal Stem Cells.

Hua J1,2, Shen N3,2, Wang J4,5,2, Tao Y4,5, Li F4,5, Chen Q4,5, Zhou X4,5.

Author information

1
Department of Radiology, 2nd Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou 310009, China.
2
These authors contributed equally to this work.
3
Department of Rheumatology, Sir Run Run Shaw Hospital, School of Medicine, Zhejiang University, Hangzhou 310016, China.
4
Department of Orthopedics Surgery, 2nd Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou 310009, China.
5
Orthopedics Research Institute of Zhejiang University, Hangzhou 310009, China.

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-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.

KEYWORDS:

Smoothened Agonist; adipose-derived mesenchymal stem cell; differentiation; nucleus pulposus; transforming growth factor-β3

PMID:
31564076
DOI:
10.14348/molcells.2019.0098
Free PMC Article

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