Tuning Thermal Dosage to Facilitate Mesenchymal Stem Cell Osteogenesis in Pro-Inflammatory Environment
Tuning Thermal Dosage to Facilitate Mesenchymal Stem Cell Osteogenesis in Pro-Inflammatory Environment
复制标题
调节热剂量以促进促炎症环境中的间充质干细胞成骨
DOI：
10.1115/1.4047660
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发表时间：
2020
期刊：
影响因子：
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通讯作者：
Wang, Sihong
中科院分区：
文献类型：
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作者：
Sunderic, Kristifor;Li, Chenghai;Ahmed, A.H. Rezwanuddin;Dawkins, Dionne;Azar, Tala;Cardoso, Luis;Wang, Sihong
间充质干细胞（MSC）是多能细胞，可以复制和分化为不同的谱系，增强其作为再生间充质组织的组成部分的用途。我们以前的工作和其他研究表明，温和的热休克促进成骨。然而，在轻度升高的温度条件下，促炎细胞因子对成骨分化的影响仍有待充分研究。在这项研究中，将人MSC（hMSC）与肿瘤坏死因子-α（TNF-α）（急性期反应的重要介质）和白细胞介素-6（IL-6）（其在破坏慢性炎症中起作用）一起培养，然后在39 °C下以不同频率进行热休克-每周1小时（低），每隔一天1小时（轻度），以及每隔一天每天3次1小时间隔（高）。DNA数据显示，周期性温和加热抑制细胞因子引起的细胞生长抑制，并诱导hMSCs的最大增殖，而高温则有相反的效果。定量成骨测定显示，与低加热或非加热对照组相比，轻度加热后成骨培养物中碱性磷酸酶（ALP）活性和钙沉淀水平显著升高。这些结果表明，周期性轻度高温可用于促进使用hMSCs的骨再生，因此可能会影响体内热疗法的设计。
Mesenchymal stem cells (MSCs) are multipotent cells that can replicate and differentiate to different lineages, potentiating their use as integral components in regenerated mesenchymal tissues. Our previous work and other studies have indicated that mild heat shock enhances osteogenesis. However, the influence of pro-inflammatory cytokines on osteogenic differentiation during mildly elevated temperature conditions remains to be fully explored. In this study, human MSCs (hMSCs) were cultured with tumor necrosis factor-alpha (TNF-α), an important mediator of the acute phase response, and interleukin-6 (IL-6) which plays a role in damaging chronic inflammation, then heat shocked at 39 °C in varying frequencies—1 h per week (low), 1 h every other day (mild), and 1 h intervals three times per day every other day (high). DNA data showed that periodic mild heating inhibited suppression of cell growth caused by cytokines and induced maximal proliferation of hMSCs while high heating had the opposite effect. Quantitative osteogenesis assays show significantly higher levels of alkaline phosphatase (ALP) activity and calcium precipitation in osteogenic cultures following mild heating compared to low heating or nonheated controls. These results demonstrate that periodic mild hyperthermia may be used to facilitate bone regeneration using hMSCs, and therefore may influence the design of heat-based therapies in vivo.