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DIFFERENTIATION OF ADIPOSE-DERIVED STEM CELLS INTO FUNCTIONAL CHONDROCYTES BY SOX9-INDUCED SMALL MOLECULE​
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  • 2019-07-02 16:04:45

ISSCR 2019: 26-29 JUNE

LOS ANGELES

(T-2014)


DIFFERENTIATION OF ADIPOSE-DERIVED STEM CELLS INTO FUNCTIONAL CHONDROCYTES BY SOX9-INDUCED SMALL MOLECULE


Lee, Jiyun - Institute for Bio-Medical Convergence, College of Medicine, Catholic Kwandong University, Incheon, Korea
Kang, Misun - Catholic Kwandong University, Institute for Bio-Medical Convergence, Incheon, Korea
Park, Jun-Hee - Institute for Bio-Medical Convergence, Catholic Kwandong University, Incheon, Korea
Song, Byeong-Wook - Institute for Bio-Medical Convergence, Catholic Kwandong University, Incheon, Korea
Lim, Soyeon - Institute for Bio-Medical Convergence, Catholic Kwandong University, Incheon, Korea
Choi, Jung-Won - Institute for Bio-Medical Convergence, Catholic Kwandong University, Incheon, Korea
Kim, Sang woo - Institute for Bio-Medical Convergence, Catholic Kwandong University, Incheon, Korea
Kim, Il-Kwon - Institute for Bio-Medical Convergence, Catholic Kwandong University, Incheon, Korea
Lee, Seahyoung - Institute for Bio-Medical Convergence, Catholic Kwandong University, Incheon, Korea
Hwang, Ki-chul - Institute for Bio-Medical Convergence, Catholic Kwandong University, Incheon, Korea

Osteoarthritis (OA) is a common joint disease that results from the disintegration of joint cartilage. Upon damage to the cartilage, chondrocytes differentiate into hypertrophic chondrocytes and release matrix-degrading enzymes leading to cartilage disintegration and calcification. Although chondrocytes have no self-renewal, there have been efforts to treat OA using stem cells, but it is difficult for stem cells to induce differentiation into chondrocyte-like cells without inducing hypertrophic chondrocyte characteristics. Therefore, an optimized method to differentiate stem cells into chondrocytes that do not display undesired phenotypes is needed. Previous studies have shown that overexpression of sox9, which is expressed during cartilage development, increases the expression of chondrocyte factors and has succeeded in differentiating stem cells into cartilage cells. Therefore, this study focused on differentiating adiposederived stem cells (ASCs) into functional chondrocytes using a small molecule that regulated the expression of Sox9 and then explored its ability to treat OA. First, the expression of Sox9 was evaluated in chondrocytes and stem cells, and a drug capable of increasing the expression of Sox9 was then selected using a GFP-Sox9 promoter vector. Drug 138(D138) was selected because it increases the Sox9 expression in candidate drugs and did not induce hypertrophic chondrocyte characteristics. Next, the recovery rate of cartilage regeneration in ASCs differentiation into chondrocytes by D138 was confirmed in a collagenase-induced animal model of OA. The group injected with ASCs-differentiated into chondrocytes by D138 recovered damaged cartilage faster than compared to the group injected with untreated ASCs. Taken together, these data confirm that D138 induces ASCs to differentiate into mature chondrocytes that do not exhibit the characteristics of hypertrophic chondrocytes, thus overcoming a problem encountered in previous studies. Additionally, the mechanism by which chondrocytes are differentiated by D138 and the recovery-inducing effect of D138-differentiated ASCs in OA was confirmed. These results indicate that D138 is a novel chondrocyte differentiation-inducing drug that shows potential as a cell therapy for OA. 

Funding Source: This study was funded by NRF-2018R1A1A1A05078230, 2017026A00-1919-BA01, and NRF-2015M3A9E6029519.

 

이전글 STRUCTURAL AND MOLECULAR-BASED DIFFERENTIAL FEATURES BY LONG TERM-INDUCED MESENCHYMAL STEM CELLS IN A RAT MODEL OF PARKINSONS DISEASE
다음글 EFFECT OF SMALL MOLECULE INDUCED BEIGE ADIPOCYTES ON CARDIOMYOCYTES AGAINST HYPOXIA/REOXYGENATION
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