medric medric
[닫기]
잠시만 기다려 주세요. 로딩중입니다.

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

Molecules and Cells 2019년 42권 9호 p.661 ~ 671
 ( Hua Jianming ) - Zhejiang University School of Medicine 2nd Affiliated Hospital Department of Radiology

 ( Shen Ning ) - Zhejiang University School of Medicine Sir Run Run Shaw Hospital Department of Rheumatology
 ( Wang Jingkai ) - Zhejiang University School of Medicine 2nd Affiliated Hospital Department of Orthopedics Surgery
 ( Tao Yiqing ) - Zhejiang University School of Medicine 2nd Affiliated Hospital Department of Orthopedics Surgery
 ( Li Fangcai ) - Zhejiang University School of Medicine 2nd Affiliated Hospital Department of Orthopedics Surgery
 ( Chen Qixin ) - Zhejiang University School of Medicine 2nd Affiliated Hospital Department of Orthopedics Surgery
 ( Zhou Xiaopeng ) - Zhejiang University School of Medicine 2nd Affiliated Hospital Department of Orthopedics Surgery

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.

키워드

adipose-derived mesenchymal stem cell; differentiation; nucleus pulposus; Smoothened Agonist; transforming growth factor-β3
원문 및 링크아웃 정보
 
등재저널 정보