关节炎症微环境对间充质干细胞的有害改变导致骨关节炎的恶化。
Detrimental alteration of mesenchymal stem cells by an articular inflammatory microenvironment results in deterioration of osteoarthritis.
机构信息
The First Affiliated Hospital, Zhejiang Chinese Medical University, Hangzhou, China.
Cell Resource Bank and Integrated Cell Preparation Center of Xiaoshan District, Hangzhou Regional Cell Preparation Center (Shangyu Biotechnology Co., Ltd), Hangzhou, China.
出版信息
BMC Med. 2023 Jun 19;21(1):215. doi: 10.1186/s12916-023-02923-6.
BACKGROUND
Articular injection of mesenchymal stem cells (MSCs) has been applied to treat knee osteoarthritis (kOA), but its clinical outcomes are controversial. This study investigated whether an articular inflammatory microenvironment (AIM) impacts MSC-based therapy in a rat model of kOA.
METHODS
The biological change of MSCs and the functional change of MSCs on chondrocytes were evaluated under AIM. The key mediator and mechanism for the AIM impact on MSC therapy were explored via gain- and loss-of-function approaches.
RESULTS
The results showed that MSCs exerted potent anti-kOA effects in vivo and in vitro, but that this therapy become chondrodestructive if a chronic AIM was present. Mechanistically, the overexpression of MMP13 in the injected MSCs via a MAPKs-AP1 signaling axis was revealed as the underlying mechanism for the detriment outcome.
CONCLUSIONS
This study thus clarifies recent clinical findings while also suggesting a means to overcome any detrimental effects of MSC-based therapy while improving its efficacy.
背景
关节内注射间充质干细胞（MSCs）已被应用于治疗膝骨关节炎（kOA），但其临床疗效存在争议。本研究旨在探讨关节炎症微环境（AIM）是否会影响 kOA 大鼠模型中的 MSC 治疗。
方法
评估 AIM 下 MSC 的生物学变化和对软骨细胞的功能变化。通过增益和失能方法探讨 AIM 对 MSC 治疗影响的关键介质和机制。
结果
结果表明，MSCs 在体内和体外均具有强大的抗 kOA 作用，但如果存在慢性 AIM，则这种治疗会导致软骨破坏。从机制上讲，通过 MAPKs-AP1 信号通路在注射的 MSC 中过度表达 MMP13 被揭示为损害结果的潜在机制。
结论
因此，本研究阐明了最近的临床发现，同时也提出了一种克服 MSC 治疗有害影响的方法，同时提高其疗效。
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