Alsalameh Saifeddin, Amin Rayya, Gemba Takefumi, Lotz Martin
Division of Arthritis Research-MEM 161, The Scripps Research Institute, La Jolla, CA 92037, USA.
Arthritis Rheum. 2004 May;50(5):1522-32. doi: 10.1002/art.20269.
To determine the presence of mesenchymal progenitor cells (MPCs) in human articular cartilage.
Primary cell cultures established from normal and osteoarthritic (OA) human knee articular cartilage were analyzed for the expression of CD105 and CD166, cell surface markers whose coexpression defines mesenchymal stem cells (MSCs) in bone marrow and perichondrium. The potential of cartilage cells to differentiate to adipogenic, osteogenic, and chondrogenic lineages was analyzed after immunomagnetic selection for CD105+/CD166+ cells and was compared with bone marrow-derived MSCs (BM-MSCs).
Up to 95% of isolated cartilage cells were CD105+ and approximately 5% were CD166+. The mean +/- SEM percentage of CD105+/CD166+ cells in normal cartilage was 3.49 +/- 1.93%. Primary cell cultures from OA cartilage contained significantly increased numbers of CD105+/CD166+ cells. Confocal microscopy confirmed the coexpression of both markers in the majority of BM-MSCs and a subpopulation of cartilage cells. Differentiation to adipocytes occurred in cartilage-derived cell cultures, as indicated by characteristic cell morphology and oil red O staining of lipid vacuoles. Osteogenesis was observed in isolated CD105+/CD166+ cells as well as in primary chondrocytes cultured in the presence of osteogenic supplements. Purified cartilage-derived CD105+/CD166+ cells did not express markers of differentiated chondrocytes. However, the cells were capable of chondrocytic differentiation and formed cartilage tissue in micromass pellet cultures.
These findings indicate that multipotential MPCs are present in adult human articular cartilage and that their frequency is increased in OA cartilage. This observation has implications for understanding the intrinsic repair capacity of articular cartilage and raises the possibility that these progenitor cells might be involved in the pathogenesis of arthritis.
确定人间质祖细胞(MPCs)在人关节软骨中的存在情况。
对从正常和骨关节炎(OA)人膝关节软骨建立的原代细胞培养物进行分析,检测CD105和CD166的表达,这两种细胞表面标志物的共表达可定义骨髓和软骨膜中的间充质干细胞(MSCs)。对CD105+/CD166+细胞进行免疫磁选后,分析软骨细胞向脂肪生成、成骨和软骨生成谱系分化的潜能,并与骨髓来源的MSCs(BM-MSCs)进行比较。
高达95%的分离软骨细胞为CD105+,约5%为CD166+。正常软骨中CD105+/CD166+细胞的平均±标准误百分比为3.49±1.93%。OA软骨的原代细胞培养物中CD105+/CD166+细胞数量显著增加。共聚焦显微镜证实,大多数BM-MSCs和一部分软骨细胞亚群中这两种标志物共表达。软骨来源的细胞培养物中出现向脂肪细胞的分化,表现为特征性的细胞形态和脂质空泡的油红O染色。在分离的CD105+/CD166+细胞以及在成骨补充剂存在下培养的原代软骨细胞中均观察到成骨现象。纯化的软骨来源的CD105+/CD166+细胞不表达分化软骨细胞的标志物。然而,这些细胞能够进行软骨细胞分化,并在微团块培养中形成软骨组织。
这些发现表明,多能MPCs存在于成人关节软骨中,且在OA软骨中的频率增加。这一观察结果对于理解关节软骨的内在修复能力具有重要意义,并增加了这些祖细胞可能参与关节炎发病机制的可能性。