Center for Stem Cell and Regenerative Medicine, Tokyo Medical and Dental University (TMDU), 1-5-45 Yushima, Bunkyo-Ku, Tokyo, 113-8510, Japan.
Stem Cell Res Ther. 2023 Sep 8;14(1):244. doi: 10.1186/s13287-023-03487-1.
Synovial fluid mesenchymal stem cells (SF-MSCs) originate in the synovium and contribute to the endogenous repair of damaged intra-articular tissues. Here, we clarified the relationship between their numbers and joint structural changes during osteoarthritis (OA) progression and investigated whether SF-MSCs had phenotypes favorable for tissue repair, even in an OA environment.
Partial medial meniscectomy (pMx) and sham surgery were performed on both knees of rats. SF and knee joints were collected from intact rats and from rats at 2, 4, and 6 weeks after surgery. SF was cultured for 1 week to calculate the numbers of colony-forming cells and colony areas. Joint structural changes were evaluated histologically to investigate their correlation with the numbers and areas of colonies. RNA sequencing was performed for SF-MSCs from intact knees and knees 4 weeks after the pMx and sham surgery.
Colony-forming cell numbers and colony areas were greater in the pMx group than in the intact and sham groups and peaked at 2 and 4 weeks, respectively. Synovitis scores showed the strongest correlation with colony numbers (R = 0.583) and areas (R = 0.456). RNA sequencing revealed higher expression of genes related to extracellular matrix binding, TGF-β signaling, and superoxide dismutase activity in SF-MSCs in the pMx group than in the sham group.
The number of SF-MSCs was most closely correlated with the severity of synovitis in this rat OA model. Tissue-reparative gene expression patterns were observed in SF-MSCs from OA knees, but not from knees without intra-articular tissue damage.
滑液间充质干细胞(SF-MSCs)起源于滑膜,并有助于关节内受损组织的内源性修复。在这里,我们阐明了它们的数量与骨关节炎(OA)进展过程中关节结构变化之间的关系,并研究了 SF-MSCs 是否具有有利于组织修复的表型,即使在 OA 环境中也是如此。
对大鼠双侧膝关节进行部分内侧半月板切除术(pMx)和假手术。分别从完整大鼠和手术后 2、4 和 6 周的大鼠收集 SF 和膝关节。SF 培养 1 周,计算集落形成细胞数量和集落面积。通过组织学评估关节结构变化,研究其与集落数量和面积的相关性。对完整膝关节和 pMx 及假手术后 4 周的膝关节 SF-MSCs 进行 RNA 测序。
pMx 组集落形成细胞数量和集落面积大于完整组和假手术组,分别在 2 周和 4 周达到峰值。滑膜炎评分与集落数量(R=0.583)和面积(R=0.456)相关性最强。RNA 测序显示 pMx 组 SF-MSCs 中与细胞外基质结合、TGF-β 信号和超氧化物歧化酶活性相关的基因表达较高。
在该大鼠 OA 模型中,SF-MSCs 的数量与滑膜炎的严重程度最密切相关。OA 膝关节 SF-MSCs 观察到组织修复基因表达模式,但无关节内组织损伤的膝关节无此模式。