We found that UCMSC had superior proliferative potential and more suppressive effects on peripheral blood mononuclear cell proliferation compared with BMMSC. The aGVHD improved dramatically after each of four infusions of UCMSC into the two patients. No adverse effects were noted. Both patients are doing well now. CONCLUSIONS. Considering that acquiring UCMSC is noninvasive, these cells would appear to be the ideal candidates for clinical cell-based therapies. This is the first report of UCMSC in a human clinical application, and this procedure seems both feasible and safe. These findings suggested that UCMSC were effective for treating aGVHD.

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 alpha1 (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.

The ease of obtaining fetal-type MSCs and their rapid proliferation make these cells ideal candidates for cell-based therapies, especially for diseases associated with immune responses, given the immunosuppressive effects of these cells. IL-6 might play an important role in the immunosuppressive effects of various stem cells.