Department of Orthopaedics and Rehabilitation Medicine, Faculty of Medical Sciences, University of Fukui, Matsuoka Shimoaizuki 23-3, Eiheiji, Fukui, 910-1193, Japan.
BMC Musculoskelet Disord. 2019 Jul 19;20(1):335. doi: 10.1186/s12891-019-2710-1.
Previous basic research and clinical studies examined the effects of mesenchymal stem cells (MSCs) on regeneration and maintenance of articular cartilage. However, our pilot study suggested that MSCs are more effective at suppressing inflammation and pain rather than promoting cartilage regeneration in osteoarthritis. Adipose tissue is considered a useful source of MSCs; it can be harvested easily in larger quantities compared with the bone marrow. The present study was designed to evaluate the anti-inflammatory, analgesic, and regenerative effects of intra-articularly injected processed lipoaspirate (PLA) cells (containing adipose-derived MSCs) on degenerative cartilage in a rat osteoarthritis model.
PLA cells were isolated from subcutaneous adipose tissue of 12-week-old female Sprague-Dawley rats. Osteoarthritis was induced by injection of monoiodoacetate (MIA). Each rat received 1 × 10 MSCs into the joint at day 7 (early injection group) and day 14 (late injection group) post-MIA injection. At 7, 14, 21 days after MIA administration, pain was assessed by immunostaining and western blotting of dorsal root ganglion (DRG). Cartilage quality was assessed macroscopically and by safranin-O and H&E staining, and joint inflammation was assessed by western blotting of the synovium.
The early injection group showed less cartilage degradation, whereas the late injection group showed cartilage damage similar to untreated OA group. The relative expression level of CGRP protein in DRG neurons was significantly lower in the two treatment groups, compared with the untreated group.
Intra-articular injection of PLA cells prevented degenerative changes in the early injection group, but had little effect in promoting cartilage repair in the late injection group. Interestingly, intra-articular injection of PLA cells resulted in suppression of inflammation and pain in both OA groups. Further studies are needed to determine the long-term effects of intra-articular injection of PLA cells in osteoarthritis.
先前的基础研究和临床研究考察了间充质干细胞(MSCs)对关节软骨再生和维持的影响。然而,我们的初步研究表明,MSCs 在抑制炎症和疼痛方面更有效,而不是在骨关节炎中促进软骨再生。脂肪组织被认为是 MSCs 的有用来源;与骨髓相比,它可以更轻松地大量采集。本研究旨在评估关节内注射经处理的脂肪抽吸物(PLA)细胞(含脂肪来源的 MSCs)对大鼠骨关节炎模型退变软骨的抗炎、镇痛和再生作用。
PLA 细胞从 12 周龄雌性 Sprague-Dawley 大鼠的皮下脂肪组织中分离出来。通过注射单碘乙酸(MIA)诱导骨关节炎。每只大鼠在 MIA 注射后第 7 天(早期注射组)和第 14 天(晚期注射组)接受 1×10 个 MSCs 关节内注射。在 MIA 给药后第 7、14、21 天,通过免疫染色和背根神经节(DRG)的 Western 印迹评估疼痛。通过番红 O 和 H&E 染色评估软骨质量,并通过滑膜的 Western 印迹评估关节炎症。
早期注射组软骨降解程度较低,而晚期注射组软骨损伤与未治疗的 OA 组相似。与未治疗组相比,两个治疗组 DRG 神经元中 CGRP 蛋白的相对表达水平明显降低。
关节内注射 PLA 细胞可预防早期注射组的退行性变化,但对晚期注射组促进软骨修复几乎没有影响。有趣的是,关节内注射 PLA 细胞可抑制两个 OA 组的炎症和疼痛。需要进一步研究确定关节内注射 PLA 细胞在骨关节炎中的长期效果。