Mesenchymal stem cells (MSC) can be isolated from different adult tissues including bone marrow, adipose tissue, cord blood and placenta. MSCs modulate the immune function of the major immune cell populations involved in alloantigen recognition and elimination, including antigen presenting cells, T cells, B cells and natural killer cells. Many clinical trials are currently underway that employ MSCs to treat human immunological diseases. However, the molecular mechanism that mediates the immunosuppressive effect of MSCs is still unclear and the safety of using MSC in patient needs further confirmation. Here, we review the cytokines that activate MSCs and the soluble factors produced by MSCs, which allow them to exert their immunosuppressive effects. We review the mechanism responsible, at least in part, for the immune suppressive effects of MSCs and highlight areas of research required for a better understanding of MSC immune modulation.

Objective: We aimed to determine the frequency of all known forms of congenital muscular dystrophy (CMD) in a large Australasian cohort. Methods:We screened 101 patients with CMD with a combination of immunofluorescence, Western blotting, and DNA sequencing to identify disease-associated abnormalities in glycosylated ␣-dystroglycan, collagen VI, laminin ␣2, ␣7-integrin, and selenoprotein.Results: A total of 45% of the CMD cohort were assigned to an immunofluorescent subgroup based on their abnormal staining pattern. Abnormal staining for glycosylated ␣-dystroglycan was present in 25% of patients, and approximately half of these had reduced glycosylated ␣-dystroglycan by Western blot. Sequencing of the FKRP, fukutin, POMGnT1, and POMT1 genes in all patients with abnormal ␣-dystroglycan immunofluorescence identified mutations in one patient for each of these genes and two patients had mutations in POMT2. Twelve percent of patients had abnormalities in collagen VI immunofluorescence, and we identified disease-causing COL6 mutations in eight of nine patients in whom the genes were sequenced. Laminin ␣2 deficiency accounted for only 8% of CMD. ␣7-Integrin staining was absent in 12 of 45 patients studied, and ITGA7 gene mutations were excluded in all of these patients. LGMD2I ϭ limb-girdle muscular dystrophy type 2I; MDC1C ϭ congenital muscular dystrophy type 1C; MEB ϭ muscle-eyebrain disease; PVDF ϭ polyvinylidene fluoride; SSCP ϭ single strand conformational polymorphism; UCMD ϭ Ullrich congenital muscular dystrophy; WWS ϭ Walker-Warburg syndrome. Conclusions:

Objective-The collagen VI muscular dystrophies, Bethlem myopathy and Ullrich congenital muscular dystrophy, form a continuum of clinical phenotypes. Glycine mutations in the triple helix have been identified in both Bethlem and Ullrich congenital muscular dystrophy, but it is not known why they cause these different phenotypes.Methods-We studied eight new patients who presented with a spectrum of clinical severity, screened the three collagen VI messenger RNA for mutations, and examined collagen VI biosynthesis and the assembly pathway.Results-All eight patients had heterozygous glycine mutations toward the N-terminal end of the triple helix. The mutations produced two assembly phenotypes. In the first patient group, collagen VI dimers accumulated in the cell but not the medium, microfibril formation in the medium was moderately reduced, and the amount of collagen VI in the extracellular matrix was not significantly altered. The second group had more severe assembly defects: some secreted collagen VI tetramers

The key to dissecting the pathogenic mechanisms of collagen VI mutations lies in detailed analysis of collagen VI biosynthesis and assembly. The majority of mutations result in secretion and deposition of structurally abnormal collagen VI. However, one A-domain mutation had no detectable effect on assembly, suggesting that it acts by compromising collagen VI interactions in the extracellular matrix of muscle.

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