Enrichment of CD146+ Adipose-Derived Stem Cells in Combination with Articular Cartilage Extracellular Matrix Scaffold Promotes Cartilage Regeneration

富集CD146+脂肪干细胞与关节软骨细胞外基质支架结合促进软骨再生

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作者:Xu Li, Weimin Guo, Kangkang Zha, Xiaoguang Jing, Mingjie Wang, Yu Zhang, Chunxiang Hao, Shuang Gao, Mingxue Chen, Zhiguo Yuan, Zhenyong Wang, Xueliang Zhang, Shi Shen, Haojiang Li, Bin Zhang, Hai Xian, Yuan Zhang, Xiang Sui, Ling Qin, Jiang Peng, Shuyun Liu, Shibi Lu, Quanyi Guo

Conclusion

Our data elucidated the function of the CD146+ ADSC subpopulation, established their role in promoting cartilage repair, and highlighted the significance of cell subpopulations as a novel therapeutic for cartilage regeneration.

Methods

CD146+ ADSCs were sorted using magnetic activated cell sorting (MACS). Cell surface markers, viability, apoptosis and proliferation were evaluated in vitro. The molecular signatures were analyzed by mRNA and protein expression profiling. By intra-articular injections of cells in a rat osteochondral defect model, we assessed the role of the specific subpopulation in cartilage microenvironment. Finally, CD146+ ADSCs were combined with articular cartilage extracellular matrix (ACECM) scaffold for long term (3, 6 months) cartilage repair.

Results

The enriched CD146+ ADSCs showed a high expression of stem cell and pericyte markers, good viability, and immune characteristics to avoid allogeneic rejection. Gene and protein expression profiles revealed that the CD146+ ADSCs had different cellular functions especially in regulation inflammation. In a rat model, CD146+ ADSCs showed a better inflammation-modulating property in the early stage of intra-articular injections. Importantly, CD146+ ADSCs exhibited good biocompatibility with the ACECM scaffold and the CD146+ cell-scaffold composites produced less subcutaneous inflammation. The combination of CD146+ ADSCs with ACECM scaffold can promote better cartilage regeneration in the long term.

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