Identification of mesenchymal progenitor cells in normal and osteoarthritic human articular cartilage
Identification of mesenchymal progenitor cells in normal and osteoarthritic human articular cartilage
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DOI：
10.1002/art.20269
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发表时间：
2004-05-01
影响因子：
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通讯作者：
Lotz, M
中科院分区：
文献类型：
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作者：
Alsalameh, S;Amin, R;Lotz, M
Objective.目的：检测人关节软骨中是否存在间充质祖细胞（MPCs）。从正常和骨关节炎（OA）的人膝关节软骨建立的原代细胞培养物进行了分析的表达CD 105和CD 166，细胞表面标志物，其共表达定义骨髓和软骨膜间充质干细胞（MSC）。通过免疫磁珠筛选CD 105 +/CD 166+细胞，分析软骨细胞向成脂、成骨和成软骨细胞系分化的潜能，并与骨髓间充质干细胞（BM-MSCs）进行比较。高达95%的分离软骨细胞为CD 105+，接近5%为CD 166+。正常软骨中CD 105 +/CD 166+细胞的平均+/- SEM百分比为3.49 +/-1.93%。来自OA软骨的原代细胞培养物含有显著增加数量的CD 105 +/CD 166+细胞。共聚焦显微镜证实了这两种标记物在大多数BM-MSCs和软骨细胞亚群中的共表达。软骨来源的细胞培养物中发生了向脂肪细胞的分化，如特征性细胞形态和脂质空泡的油红O染色所示。在分离的CD 105 +/CD 166+细胞以及在成骨补充剂存在下培养的原代软骨细胞中观察到成骨作用。纯化的软骨来源的CD 105 +/CD 166+细胞不表达分化的软骨细胞的标志物。但在微团培养中，细胞具有向软骨细胞分化的能力，并可形成软骨组织。这些发现表明，多能MPC存在于成人关节软骨中，并且其频率在OA软骨中增加。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，并提出了这些祖细胞可能参与关节炎发病机制的可能性。
Objective. To determine the presence of mesenchymal progenitor cells (MPCs) in human articular cartilage.Methods. 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).Results. Up to 95% of isolated cartilage cells were CD105+ and similar to5% 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.Conclusion. 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.