Poor potential of proliferation and differentiation in bone marrow mesenchymal stem cells derived from children with severe aplastic anemia
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The pathogenesis of severe aplastic anemia (SAA) has not been completely understood, and insufficiency of the hematopoietic microenvironment can be an important factor. Here, we compared the basic properties of mesenchymal stem cells (MSCs), a major component of bone marrow microenvironment, from five SAA children with those of MSCs from five controls. Although MSCs from SAA children and controls were similar in morphology and immunophenotypic profile, SAA MSCs had slower expansion rate and smaller cumulative population doubling (1.83 ± 1.21 vs 3.36 ± 0.87; p = 0.046), indicating lower proliferative capacity. After osteogenic induction, SAA MSCs showed lower alkaline phosphatase activity (optical density, 1.46 ± 0.04 vs 2.27 ± 0.32; p = 0.013), less intense von Kossa staining, and lower gene expression of core binding factor α1 (0.0015 ± 0.0005 vs 0.0056 ± 0.0017; p = 0.013). Following adipogenic induction, SAA MSCs showed less intense Oil red O staining (optical density, 0.86 ± 0.22 vs 1.73 ± 0.42; p = 0.013) and lower lipoprotein lipase expression (0.0105 ± 0.0074 vs 0.0527 ± 0.0254; p = 0.013). These findings provided evidence that defects in bone marrow MSCs of SAA children do exist.
KeywordsAplastic anemia Mesenchymal stem cells Hematopoiesis Bone marrow failure Microenvironment
This work was supported partially by grants from the China Medical University Hospital (grant ref. NO. DMR-98-037) and Taoyuan General Hospital Project (PTH9809).
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