Open AccessProgrammed Application of Transforming Growth Factor β3 and Rac1 Inhibitor NSC23766 Committed Hyaline Cartilage Differentiation of Adipose‐Derived Stem Cells for Osteochondral Defect Repair
Author(s) -
Zhu Shouan,
Chen Pengfei,
Wu Yan,
Xiong Si,
Sun Heng,
Xia Qingqing,
Shi Libing,
Liu Huanhuan,
Ouyang Hong Wei
Publication year - 2014
Publication title -
stem cells translational medicine
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.781
H-Index - 71
eISSN - 2157-6580
pISSN - 2157-6564
DOI - 10.5966/sctm.2014-0042
Subject(s) - chondrogenesis , microbiology and biotechnology , cartilage , hyaline cartilage , stem cell , rac1 , biology , cellular differentiation , anatomy , pathology , medicine , osteoarthritis , signal transduction , biochemistry , alternative medicine , gene , articular cartilage
Hyaline cartilage differentiation is always the challenge with application of stem cells for joint repair. Transforming growth factors (TGFs) and bone morphogenetic proteins can initiate cartilage differentiation but often lead to hypertrophy and calcification, related to abnormal Rac1 activity. In this study, we developed a strategy of programmed application of TGFβ3 and Rac1 inhibitor NSC23766 to commit the hyaline cartilage differentiation of adipose‐derived stem cells (ADSCs) for joint cartilage repair. ADSCs were isolated and cultured in a micromass and pellet culture model to evaluate chondrogenic and hypertrophic differentiation. The function of Rac1 was investigated with constitutively active Rac1 mutant and dominant negative Rac1 mutant. The efficacy of ADSCs with programmed application of TGFβ3 and Rac1 inhibitor for cartilage repair was studied in a rat model of osteochondral defects. The results showed that TGFβ3 promoted ADSCs chondro‐lineage differentiation and that NSC23766 prevented ADSC‐derived chondrocytes from hypertrophy in vitro. The combination of ADSCs, TGFβ3, and NSC23766 promoted quality osteochondral defect repair in rats with much less chondrocytes hypertrophy and significantly higher International Cartilage Repair Society macroscopic and microscopic scores. The findings have illustrated that programmed application of TGFβ3 and Rac1 inhibitor NSC23766 can commit ADSCs to chondro‐lineage differentiation and improve the efficacy of ADSCs for cartilage defect repair. These findings suggest a promising stem cell‐based strategy for articular cartilage repair.