Adipose-derived mesenchymal stem cells with hypoxic preconditioning improve tenogenic differentiation

作者：Xing Guo, Denghua Huang, Dan Li, Longfei Zou, Hui Lv, Yuanhui Wang, Meiyun Tan · 发表于：Journal of Orthopaedic Surgery and Research · 年份：2022 · DOI：10.1186/s13018-021-02908-2 · 被引用次数：17 · 研究领域：Cancer, Hypoxia, and Metabolism、Mesenchymal stem cell research、Cancer Cells and Metastasis

Abstract Background Adipose-derived mesenchymal stem cells (ADSCs), as seed cells for tendon tissue engineering, are promising for tendon repair and regeneration. But for ADSCs, diverse oxygen tensions have different stimulatory effects. To explore this issue, we investigated the tenogenic differentiation capability of ADSCs under hypoxia condition (5% O 2 ) and the possible signaling pathways correspondingly. The effects of different oxygen tensions on proliferation, migration, and tenogenic differentiation potential of ADSCs were investigated. Methods P4 ADSCs were divided into a hypoxic group and a normoxic group. The hypoxic group was incubated under a reduced O 2 pressure (5% O 2 , 5% CO 2 , balanced N 2 ). The normoxic group was cultured in 21% O 2 . Two groups were compared: HIF-1α inhibitor (2-MeOE2) in normoxic culturing conditions and hypoxic culturing conditions. Hypoxia-inducible factor-1α (HIF-1α) and VEGF were measured using RT-qPCR. Specific HIF-1α inhibitor 2-methoxyestradiol (2-MeOE2) was applied to investigate whether HIF-1α involved in ADSCs tenogenesis under hypoxia. Results Hypoxia significantly reduced proliferation and migration of ADSCs. Continuous treatment of ADSCs at 5% O 2 resulted in a remarkable decrease in HIF-1α expression in comparison with 20% O 2 . Additionally, ADSCs of hypoxia preconditioning exhibited higher mRNA expression levels of the related key tenogenic makers and VEGF than normoxia via RT-qPCR measurement ( p ˂ 0.05). Furthermore, ...