Osteoarticular and Aging Research Lab, Cellular Therapy Unit, INIBIC-CH Universitario Juan Canalejo, 15006 A Coruña, Spain.
J Cell Biochem. 2010 Nov 1;111(4):834-45. doi: 10.1002/jcb.22768.
In this study we analyzed the chondrogenic potential of subpopulations of mesenchymal stem cells (MSCs) derived from human synovial membranes enriched for CD73, CD106, and CD271 markers. Subpopulations of human synovial membrane MSCs enriched for CD73, CD106, and CD271 markers were isolated using a cytometry sorter and characterized by flow cytometry for MSC markers. The expression of Sox9, Nanog, and Runx2 genes by these cells was measured by reverse transcriptase-polymerase chain reaction. The chondrogenesis of each subpopulation was assessed by culturing the cells in a defined medium to produce spontaneous spheroid formation and differentiation towards chondrocyte-like cells. The examination of the spheroids by histological and immunohistochemical analyses for collagen type II (COL2), aggrecan, collagen type I (COL1), metalloprotease 13 (MMP13), and collagen type X (COLX) levels were performed to assess their chondrogenesis capacity. The adipogenesis and osteogenesis potential of each subpopulation was determined using commercial media; the resulting cells were stained with oil red O or red alizarin to test the degree of differentiation. The subpopulations had different profiles of cells positive for the MSC markers CD44, CD69, CD73, CD90, and CD105 and showed different expression levels of the genes Sox9, Nanog, and Runx2 involved in chondrogenesis, undifferentiation, and osteoblastogenesis, respectively. Immunohistochemical analysis demonstrated that COL1, COL2, COLX, MMP13, and aggrecan were expressed in the spheroids as soon as 14 days of culture. The CD271(+) subpopulation expressed the highest levels of COL2 staining compared to the other subpopulations. CD105 and Runx2 were shown by immunohistochemistry and genetic analysis to have significantly higher expression CD271(+) subpopulation than the other subpopulations. Spheroids formed from CD271-enriched and CD73-enriched MSCs from normal human synovial membranes mimic the native cartilage extracellular matrix more closely than CD106(+) MSCs and are possible candidates for use in cartilage tissue engineering. Both cell types have potential for promoting the differentiation of MSCs into chondrocytes, presenting new possibilities for achieving intrinsic cartilage repair.
在这项研究中,我们分析了从富含 CD73、CD106 和 CD271 标志物的人滑膜中分离的间充质干细胞(MSC)亚群的软骨形成潜力。使用细胞分选仪分离富含 CD73、CD106 和 CD271 标志物的人滑膜 MSC 亚群,并通过流式细胞术对 MSC 标志物进行特征分析。通过逆转录聚合酶链反应测量这些细胞中 Sox9、Nanog 和 Runx2 基因的表达。通过在定义培养基中培养细胞来评估每个亚群的软骨形成,以产生自发的球体形成并向软骨细胞样细胞分化。通过组织学和免疫组织化学分析评估球体中胶原蛋白 II (COL2)、聚集蛋白聚糖、胶原蛋白 I (COL1)、金属蛋白酶 13 (MMP13) 和胶原蛋白 X (COLX) 水平来评估其软骨形成能力。使用商业培养基确定每个亚群的成脂和成骨潜力;用油红 O 或红色茜素染色检测分化程度。亚群对 MSC 标志物 CD44、CD69、CD73、CD90 和 CD105 的阳性细胞具有不同的表达谱,并表现出不同水平的 Sox9、Nanog 和 Runx2 基因的表达,这些基因分别参与软骨形成、未分化和成骨细胞形成。免疫组织化学分析表明,COL1、COL2、COLX、MMP13 和聚集蛋白聚糖在培养 14 天内即存在于球体中。与其他亚群相比,CD271(+) 亚群的 COL2 染色表达水平最高。免疫组织化学和基因分析表明,与其他亚群相比,CD271(+) 亚群的 CD105 和 Runx2 表达水平显著更高。来自正常人类滑膜的富含 CD271 和 CD73 的 MSC 形成的球体比 CD106(+) MSC 更接近天然软骨细胞外基质,可能是软骨组织工程的候选物。这两种细胞类型都有可能促进 MSC 向软骨细胞分化,为实现内在软骨修复提供了新的可能性。