Periodic heat shock accelerated the chondrogenic differentiation of human mesenchymal stem cells in pellet culture.
Periodic heat shock accelerated the chondrogenic differentiation of human mesenchymal stem cells in pellet culture.
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DOI：
10.1371/journal.pone.0091561
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发表时间：
2014
期刊：
影响因子：
3.7
通讯作者：
Wang S
中科院分区：
文献类型：
--
作者：
Chen J;Li C;Wang S
骨关节炎是严重影响老年人生活质量的疾病之一。人骨髓间充质干细胞（hMSCs）为骨关节炎患者的关节修复提供了潜在的希望。然而，体外从hMSC向软骨细胞的分化需要很长时间（约16周），并且分化的细胞仍然不如原代分离的软骨细胞功能成熟，尽管已经深入研究了化学刺激和机械负荷以增强hMSC分化。另一方面，hMSC软骨形成的热刺激尚未得到很好的探索。本研究探讨了轻度热休克（HS）对hMSCs在三维颗粒培养中向软骨细胞分化的直接影响。在软骨形成的第10天，在41°C下持续1小时的周期性HS显著增加了3D团块培养物中的硫酸化糖胺聚糖。免疫组织化学和Western印迹分析显示，在软骨形成的第17天，热休克颗粒中II型胶原和聚集蛋白聚糖的表达比非热休克颗粒增加。此外，HS还上调分化第17天和第24天的I型和X型胶原以及热休克蛋白70的表达。这些结果表明，HS加速了hMSCs的软骨分化，并诱导从hMSCs分化的软骨细胞的早期成熟。这项研究的结果将指导未来使用热处理促进人类间充质干细胞软骨再生的方案的设计。
Osteoarthritis (OA) is one of diseases that seriously affect elderly people's quality of life. Human mesenchymal stem cells (hMSCs) offer a potential promise for the joint repair in OA patients. However, chondrogenic differentiation from hMSCs in vitro takes a long time (∼6 weeks) and differentiated cells are still not as functionally mature as primary isolated chondrocytes, though chemical stimulations and mechanical loading have been intensively studied to enhance the hMSC differentiation. On the other hand, thermal stimulations of hMSC chondrogenesis have not been well explored. In this study, the direct effects of mild heat shock (HS) on the differentiation of hMSCs into chondrocytes in 3D pellet culture were investigated. Periodic HS at 41°C for 1 hr significantly increased sulfated glycosaminoglycan in 3D pellet culture at Day 10 of chondrogenesis. Immunohistochemical and Western Blot analyses revealed an increased expression of collagen type II and aggrecan in heat-shocked pellets than non heat-shocked pellets on Day 17 of chondrogenesis. In addition, HS also upregulated the expression of collagen type I and X as well as heat shock protein 70 on Day 17 and 24 of differentiation. These results demonstrate that HS accelerated the chondrogenic differentiation of hMSCs and induced an early maturation of chondrocytes differentiated from hMSCs. The results of this study will guide the design of future protocols using thermal treatments to facilitate cartilage regeneration with human mesenchymal stem cells.
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