期刊
STEM CELLS TRANSLATIONAL MEDICINE
卷 3, 期 10, 页码 1242-1251出版社
ALPHAMED PRESS
DOI: 10.5966/sctm.2014-0042
关键词
Adipose-derive stem cells; Rac1; Osteochondral defect; Hypertrophy
资金
- National Program on Key Basic Research project [2012CB966604]
- National Natural Science Fund [81125014, 81101356, 81201395, 31000436]
- Zhejiang Province Public Welfare Fund [2012C3112]
- Zhejiang Provincial Natural Science Foundation of China [LY13C100001]
- Postdoctoral Foundation of China [2013M531465]
- Regenerative Medicine in Innovative Medical Subjects of Zhejiang Province
- Zhejiang Provincial Program for the Cultivation of High-Level Innovative Health Talents
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 TGF beta 3 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 TGF beta 3 and Rac1 inhibitor for cartilage repair was studied in a rat model of osteochondral defects. The results showed that TGF beta 3 promoted ADSCs chondro-lineage differentiation and that NSC23766 prevented ADSC-derived chondrocytes from hypertrophy in vitro. The combination of ADSCs, TGF beta 3, 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 TGF beta 3 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.
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