Jones Elena A, Crawford Aileen, English Anne, Henshaw Karen, Mundy Jenifer, Corscadden Diane, Chapman Tony, Emery Paul, Hatton Paul, McGonagle Dennis
University of Leeds, Leeds, UK.
Arthritis Rheum. 2008 Jun;58(6):1731-40. doi: 10.1002/art.23485.
Arthritic synovial fluid (SF) contains mesenchymal stem cells (MSCs), which could simply reflect their shedding from diseased joint structures. This study used the bovine model to explore SF MSCs in health and enumerated them at the earliest stages of human osteoarthritis (OA) in radiographically normal joints.
Clonogenicity and multipotentiality of normal bovine SF MSCs were compared with donor-matched bone marrow (BM) MSCs at the single-cell level. The colony-forming unit-fibroblastic assay was used for MSC enumeration. The XTT assay was employed to assess cell proliferation, and flow cytometry was used to investigate the marker phenotype of bovine and human SF MSCs.
Single MSCs were present in normal bovine SF, and 96% of them were able to expand at least 1 million-fold. These cells were CD271-, multipotential, considerably more clonogenic, and less adipogenic than matched BM MSCs. In both pellet assays and on polyglycolic acid scaffolds, SF clones displayed consistent chondrogenic differentiation, while BM clones were variable. MSCs were present in arthroscopically normal human joints and were increased 7-fold in early OA (P = 0.034). Their numbers correlated with numbers of free microscopic synovial tissue fragments (r = 0.826, P < 0.0001). OA SF had a growth-promoting effect on synovial MSCs.
This study confirms the presence of MSCs in normal SF and shows their numerical increase in early human OA. SF MSCs are likely to originate from synovium. These findings provide a platform for the exploration of the potential role of SF MSCs in joint homeostasis and for investigation of their utility in novel joint regeneration strategies.
关节炎性滑液（SF）中含有间充质干细胞（MSC），这可能仅仅反映了它们从患病关节结构中脱落的情况。本研究使用牛模型来探索健康状态下的SF MSC，并在人类骨关节炎（OA）早期且影像学检查正常的关节中对其进行计数。
在单细胞水平上，将正常牛SF MSC的克隆形成能力和多能性与供体匹配的骨髓（BM）MSC进行比较。采用集落形成单位-成纤维细胞试验对MSC进行计数。使用XTT试验评估细胞增殖，并用流式细胞术研究牛和人类SF MSC的标志物表型。
正常牛SF中存在单个MSC，其中96%能够扩增至少100万倍。这些细胞CD271阴性、具有多能性，与匹配的BM MSC相比，克隆形成能力更强，脂肪生成能力较弱。在沉淀试验和聚乙醇酸支架上，SF克隆均表现出一致的软骨形成分化，而BM克隆则存在差异。在关节镜检查正常的人类关节中存在MSC，在早期OA中其数量增加了7倍（P = 0.034）。它们的数量与游离微观滑膜组织碎片的数量相关（r = 0.826，P < 0.0001）。OA SF对滑膜MSC有促生长作用。
本研究证实了正常SF中存在MSC，并显示其在人类OA早期数量增加。SF MSC可能起源于滑膜。这些发现为探索SF MSC在关节稳态中的潜在作用以及研究其在新型关节再生策略中的效用提供了一个平台。
