Desando Giovanna, Cavallo Carola, Sartoni Federica, Martini Lucia, Parrilli Annapaola, Veronesi Francesca, Fini Milena, Giardino Roberto, Facchini Andrea, Grigolo Brunella
Arthritis Res Ther. 2013 Jan 29;15(1):R22. doi: 10.1186/ar4156.
Cell therapy is a rapidly growing area of research for the treatment of osteoarthritis (OA). This work is aimed to investigate the efficacy of intra-articular adipose-derived stromal cell (ASC) injection in the healing process on cartilage, synovial membrane and menisci in an experimental rabbit model.
The induction of OA was performed surgically through bilateral anterior cruciate ligament transection (ACLT) to achieve eight weeks from ACLT a mild grade of OA. A total of 2×10⁶ and 6×10⁶ autologous ASCs isolated from inguinal fat, expanded in vitro and suspended in 4% rabbit serum albumin (RSA) were delivered in the hind limbs; 4% RSA was used as the control. Local bio-distribution of the cells was verified by injecting chloro-methyl-benzamido-1,1'-dioctadecyl-3,3,3'3'-tetra-methyl-indo-carbocyanine per-chlorate (CM-Dil) labeled ASCs in the hind limbs. Cartilage and synovial histological sections were scored by Laverty's scoring system to assess the severity of the pathology. Protein expression of some extracellular matrix molecules (collagen I and II), catabolic (metalloproteinase-1 and -3) and inflammatory (tumor necrosis factor- α) markers were detected by immunohistochemistry. Assessments were carried out at 16 and 24 weeks.
Labeled-ASCs were detected unexpectedly in the synovial membrane and medial meniscus but not in cartilage tissue at 3 and 20 days from ASC-treatment. Intra-articular ASC administration decreases OA progression and exerts a healing contribution in the treated animals in comparison to OA and 4% RSA groups.
Our data reveal a healing capacity of ASCs in promoting cartilage and menisci repair and attenuating inflammatory events in synovial membrane inhibiting OA progression. On the basis of the local bio-distribution findings, the benefits obtained by ASC treatment could be due to a trophic mechanism of action by the release of growth factors and cytokines.
细胞疗法是治疗骨关节炎（OA）的一个快速发展的研究领域。本研究旨在探讨在实验性兔模型中，关节腔内注射脂肪来源的间充质干细胞（ASC）对软骨、滑膜和半月板愈合过程的疗效。
通过双侧前交叉韧带切断术（ACLT）手术诱导OA，在ACLT后8周达到轻度OA。从腹股沟脂肪中分离出的总共2×10⁶和6×10⁶自体ASC，在体外扩增并悬浮于4%兔血清白蛋白（RSA）中，注入后肢；4% RSA用作对照。通过在兔后肢注射氯甲基苯甲酰胺-1,1'-二十八烷基-3,3,3'3'-四甲基吲哚羰花青高氯酸盐（CM-Dil）标记的ASC来验证细胞的局部生物分布。软骨和滑膜组织学切片采用Laverty评分系统进行评分，以评估病理严重程度。通过免疫组织化学检测一些细胞外基质分子（胶原蛋白I和II）、分解代谢（金属蛋白酶-1和-3）和炎症（肿瘤坏死因子-α）标志物的蛋白表达。在第16周和第24周进行评估。
在ASC治疗后3天和20天，在滑膜和内侧半月板中意外检测到标记的ASC，但在软骨组织中未检测到。与OA组和4% RSA组相比，关节腔内给予ASC可减少OA进展，并对治疗动物发挥愈合作用。
我们的数据揭示了ASC在促进软骨和半月板修复以及减轻滑膜炎症事件、抑制OA进展方面的愈合能力。基于局部生物分布结果，ASC治疗所获得的益处可能归因于生长因子和细胞因子释放的营养作用机制。
