Jiang Hao, Chen Jiafang, Lin Zhangya, Liao Naishun
Department of Pain Medicine, The First Affiliated Hospital of Fujian Medical University, Fuzhou, 350000 People's Republic of China.
National Regional Medical Center, Binhai Campus of the First Affiliated Hospital, Fujian Medical University, Fuzhou, 350212 People's Republic of China.
Cytotechnology. 2024 Oct;76(5):547-558. doi: 10.1007/s10616-024-00635-0. Epub 2024 Jun 8.
Although adipose tissue-derived mesenchymal stem cell (ADSC) transplantation has been effectively used to treat osteoarthritis (OA), the low cell survival rate induced by the inflammatory and oxidative stress, severely affects the therapeutic efficiency of ADSC transplantation in OA. This study was designed to evaluate whether melatonin pretreatment could improve ADSC survival and its therapeutic efficacy in OA. The papain-induced OA rats were pretreated with melatonin via intra-articular injection and then intra-articular injected with indocyanine green (ICG)-labeled ADSCs (3 × 10/rat). Afterward, ADSC retention was evaluated by NIR-II fluorescence imaging. The tibia and synovial fluid were collected for histopathological examination and ELISA assay, respectively. To confirm the anti-inflammatory effect of melatonin, a TNF-α and IL-1β-induced cell model was used to evaluate the protective effects of melatonin on ADSC viability, cell apoptosis, and migration. Our results showed that melatonin pretreatment enhanced ADSC survival and improved the therapeutic effects of ADSC transplantation on cartilage repair, and anti-inflammation by reducing TNF-α, IL-6, IL-1β, and IL-12 in vivo. In particular, we also found that melatonin promoted ADSC viability and migration, and reduced cell apoptosis in vitro. In conclusion, this study supports that melatonin pretreatment can effectively improve ADSC survival and therapeutic efficiency in OA by reducing inflammatory injuries, which provides a novel strategy for enhancing ADSC therapy.
尽管脂肪组织来源的间充质干细胞（ADSC）移植已被有效用于治疗骨关节炎（OA），但炎症和氧化应激诱导的低细胞存活率严重影响了ADSC移植治疗OA的疗效。本研究旨在评估褪黑素预处理是否能提高ADSC在OA中的存活率及其治疗效果。采用木瓜蛋白酶诱导的OA大鼠，通过关节内注射褪黑素进行预处理，然后关节内注射吲哚菁绿（ICG）标记的ADSCs（3×10/只大鼠）。之后，通过近红外二区荧光成像评估ADSC的留存情况。分别收集胫骨和滑液进行组织病理学检查和ELISA检测。为了证实褪黑素的抗炎作用，使用肿瘤坏死因子-α（TNF-α）和白细胞介素-1β（IL-1β）诱导的细胞模型来评估褪黑素对ADSC活力、细胞凋亡和迁移的保护作用。我们的结果表明，褪黑素预处理提高了ADSC的存活率，改善了ADSC移植对软骨修复的治疗效果，并通过降低体内TNF-α、IL-6、IL-1β和IL-12发挥抗炎作用。特别是，我们还发现褪黑素在体外促进了ADSC的活力和迁移，并减少了细胞凋亡。总之，本研究支持褪黑素预处理可通过减少炎症损伤有效提高ADSC在OA中的存活率和治疗效率，为增强ADSC治疗提供了一种新策略。
